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BACKGROUNDPreclinical studies suggest that cholesterol accumulation leads to insulin resistance. We previously reported that alterations in a monocyte cholesterol metabolism transcriptional network (CMTN) - suggestive of cellular cholesterol accumulation - were cross-sectionally associated with obesity and type 2 diabetes (T2D). Here, we sought to determine whether the CMTN alterations independently predict incident prediabetes/T2D risk, and correlate with cellular cholesterol accumulation.METHODSMonocyte mRNA expression of 11 CMTN genes was quantified among 934 Multi-Ethnic Study of Atherosclerosis (MESA) participants free of prediabetes/T2D; cellular cholesterol was measured in a subset of 24 monocyte samples.RESULTSDuring a median 6-year follow-up, lower expression of 3 highly correlated LXR target genes - ABCG1 and ABCA1 (cholesterol efflux) and MYLIP (cholesterol uptake suppression) - and not other CMTN genes, was significantly associated with higher risk of incident prediabetes/T2D. Lower expression of the LXR target genes correlated with higher cellular cholesterol levels (e.g., 47% of variance in cellular total cholesterol explained by ABCG1 expression). Further, adding the LXR target genes to overweight/obesity and other known predictors significantly improved prediction of incident prediabetes/T2D.CONCLUSIONThese data suggest that the aberrant LXR/ABCG1-ABCA1-MYLIP pathway (LAAMP) is a major T2D risk factor and support a potential role for aberrant LAAMP and cellular cholesterol accumulation in diabetogenesis.FUNDINGThe MESA Epigenomics and Transcriptomics Studies were funded by NIH grants 1R01HL101250, 1RF1AG054474, R01HL126477, R01DK101921, and R01HL135009. This work was supported by funding from NIDDK R01DK103531 and NHLBI R01HL119962.

BACKGROUND: Artemisinin resistance in Plasmodium falciparum threatens global malaria elimination efforts. To contain and then eliminate artemisinin resistance in Eastern Myanmar a network of community-based malaria posts was instituted and targeted mass drug administration (MDA) with dihydroartemisinin-piperaquine (three rounds at monthly intervals) was conducted. The prevalence of artemisinin resistance during the elimination campaign (2013-2019) was characterized. METHODS: Throughout the six-year campaign Plasmodium falciparum positive blood samples from symptomatic patients and from cross-sectional surveys were genotyped for mutations in kelch-13-a molecular marker of artemisinin resistance. RESULT: The program resulted in near elimination of falciparum malaria. Of 5162 P. falciparum positive blood samples genotyped, 3281 (63.6%) had K13 mutations. The prevalence of K13 mutations was 73.9% in 2013 and 64.4% in 2019. Overall, there was a small but significant decline in the proportion of K13 mutants (p

Farming sustainably and protecting gross harvest production correctly provides growers with “health care, school fees and peace-of-mind” (net benefits). Reducing Postharvest and input loss sustains the components of agriculture’s triple-bottom-line which are “accessible nutrition, reduced green-house emissions, and foreign exchange reserves”. Lacking storage that stops grain PHL, agriculture suffers critical problems like the Aspergillus fungi that leaves grain contaminated with invisible aflatoxin that growers cannot consume or market. The objective of the Ghana pilot study was to understand why new ideas/findings like, applying biologicals to the soil before harvest, gross production inputs, virtual markets and especially the spread of stationary grain warehouses have failed to improve the net benefits of farming or agricultures’ triple-bottomline in sub-Saharan Africa. Qualitative comparison methods were used to identify roadblocks to improvement as scientific monitoring and storage eliminate grain Postharvest loss on the drylands in many parts of the world. Observations suggest net benefits are being ignored as reviews and assessments of primitive or council storage exchange scientific rigor for Stationary Warehouse Prejudice. Scientific rigor illuminates how the qualitative cost of aflatoxin, and quantitative expense of pests, recycling plastic, and empty stationary warehouses impact enduser- cost per unit stored per month. We conclude that Postharvest loss is expensive, and that relatively inexpensive mobile metal storage assets would improve net benefits and the triple-bottom-line.

When strongly pumped at twice their resonant frequency, nonlinear resonators develop a high-amplitude intracavity field, a phenomenon known as parametric self-oscillations. The boundary over which this instability occurs can be extremely sharp and thereby presents an opportunity for realizing a detector. Here, we operate such a device based on a superconducting microwave resonator whose nonlinearity is engineered from kinetic inductance. The device indicates the absorption of low-power microwave wavepackets by transitioning to a self-oscillating state. Using calibrated pulses, we measure the detection efficiency to zeptojoule energy wavepackets. We then apply it to measurements of electron spin resonance, using an ensemble of 209Bi donors in silicon that are inductively coupled to the resonator. We achieve a latched readout of the spin signal with an amplitude that is five hundred times greater than the underlying spin echoes.

We investigate twisted bilayer graphene (TBG) at filling ν=-3 in the presence of realistic heterostrain. Strain amplifies the band dispersion and drives the system beyond the strong-coupling regime of previous theoretical studies. We use DMRG to conduct an unbiased, large-scale numerical calculations that include all spin and valley degrees of freedom, up to bond dimension χ=24576. We establish a global phase diagram that unifies a number of theoretical and experimental results. Near zero strain we find an intervalley-coherent quantized anomalous Hall (QAH-IVC) state, a competitive strong-coupling order that evaded past numerical studies. A tiny strain around 0.05% drives a transition into an incommensurate Kekulé spiral (IKS) phase, supporting the mean-field prediction in [Kwan, Phys. Rev. X 11, 041063 (2021)2160-330810.1103/PhysRevX.11.041063]. Even higher strains above 0.2% favor a flavor-symmetric metallic order, which may explain metals found at ν=-3 in many experiments.

BackgroundYemen continues to endure cholera outbreaks during ongoing conflict and destructive environmental events. Air raids have been used throughout the conflict to target military and civilian infrastructure. We aimed to assess the association between air raids and cholera incidence while taking into account geographical, environmental, economic, and demographic factors that drive outbreaks.MethodsIn this ecological modelling study, we used data from Sept 12, 2016, to Dec 29, 2019, for the number of air raids, vegetation coverage, surface water, precipitation, temperature, economic variables, and cholera case and population data to model the association between conflict and the weekly incidence of cholera (per 100 000 people) in Yemen. Data were transformed into weekly intervals and governorates were categorised according to air raid severity (the number of raids in the previous 3 months). We used a negative binomial generalised additive model that accounted for geographical location and environmental, temporal, economic, and demographic variables to estimate incidence rate ratios for the association between air raid severity and cases of cholera.FindingsDuring the study period, 2 107 912 cases of cholera were reported in Yemen, and a minimum of 11 366 air raids were recorded. After controlling for relevant factors, compared with no air raids, all other levels of air raid severity were significantly associated with cholera incidence. The largest effect was noted in governorates with severe air raid levels (ie, ≥76 during the previous 3 months), which had an incidence rate ratio of 2·06 (95% CI 1·59-2·69; p

Original citation: J Clin Invest. 2024; 134(10):e173278. https://doi.org/10.1172/JCI173278. Citation for this corrigendum: J Clin Invest. 2024;134(16):e185290. https://doi.org/10.1172/JCI185290 During the preparation of this manuscript, Daniel Duprez's information was inadvertently omitted from [...]

BackgroundInsecticide-treated net (ITN) use is among the most recommended strategies to prevent malaria in pregnancy. We analysed the regional and socio-economic patterns of ITN use among pregnant women in Kenya using data from the 2003, 2008 and 2014 Kenyan Demographic and Health Surveys (KDHSs).MethodsInequality was assessed using four dimensions: economic status, education, place of residence and region. Both relative and absolute summary measures were applied. In addition, simple and complex summary measures, i.e. difference, population attributable fraction, population attributable risk and ratio were considered based on the number of subgroups in each variable.ResultsThere was overt inequality in the use of ITNs among pregnant women, with greater use among the better-off group in 2003 and 2014. Greater ITN use was also observed among pregnant women with a higher level of education. Pregnant women from urban settings tended to use ITNs (slept under a net the night before the survey) more than their rural counterparts in the 2003 KDHS. There were significant regional variations across the three surveys in all inequality summary measures, except ratio in the 2014 survey.ConclusionsSignificant inequality in ITN use among pregnant women was observed at a macro scale.

Combining genomic and geospatial data can be useful for understanding Mycobacterium tuberculosis transmission in high-burden tuberculosis (TB) settings. We performed whole-genome sequencing on M. tuberculosis DNA extracted from sputum cultures from a population-based TB study conducted in Gaborone, Botswana, during 2012-2016. We determined spatial distribution of cases on the basis of shared genotypes among isolates. We considered clusters of isolates with ≤5 single-nucleotide polymorphisms identified by whole-genome sequencing to indicate recent transmission and clusters of ≥10 persons to be outbreaks. We obtained both molecular and geospatial data for 946/1,449 (65%) participants with culture-confirmed TB; 62 persons belonged to 5 outbreaks of 10-19 persons each. We detected geospatial clustering in just 2 of those 5 outbreaks, suggesting heterogeneous spatial patterns. Our findings indicate that targeted interventions applied in smaller geographic areas of high-burden TB identified using integrated genomic and geospatial data might help interrupt TB transmission during outbreaks.

Despite global investments in malaria eradication and mitigation efforts, including the dissemination of ITNs to vulnerable communities, the goal of widespread malaria control among pregnant women has yet to be realized in many African countries. One of the explanations forwarded for this is related to the adoption and regular use of ITNs by pregnant women. Based on the available DHS and MIS data from four malaria high burden African countries- according to WHO malaria report 2020- inequality was measured by applying both relative and absolute summary measures for the four dimensions of inequality: economic status, education, place of residence and region. By considering the number of subgroups in each variable, simple and complex summary measures were used.ITN utilization by pregnant women showed an increasing trend over time in all the four countries. There was also significant inequality (variability) in the ITN utilization among population groups. DRC, Mozambique and Uganda showed noticeable inequality that favors the richest population, whereas in Nigeria the inequality was observed among both the rich and the poor during different survey yearsIn conclusion, in all the four countries, there were significant regional variations or differences in ITN use among pregnant mothers across all dimensions of inequality in the survey years. Tailored cost-effective interventions could be considered to improve ITN utilization among pregnant women.

Mechanistic models fit to streaming surveillance data are critical to understanding the transmission dynamics of an outbreak as it unfolds in real-time. However, transmission model parameter estimation can be imprecise, and sometimes even impossible, because surveillance data are noisy and not informative about all aspects of the mechanistic model. To partially overcome this obstacle, Bayesian models have been proposed to integrate multiple surveillance data streams. We devised a modeling framework for integrating SARS-CoV-2 diagnostics test and mortality time series data, as well as seroprevalence data from cross-sectional studies, and tested the importance of individual data streams for both inference and forecasting. Importantly, our model for incidence data accounts for changes in the total number of tests performed. We model the transmission rate, infection-to-fatality ratio, and a parameter controlling a functional relationship between the true case incidence and the fraction of positive tests as time-varying quantities and estimate changes of these parameters nonparametrically. We compare our base model against modified versions which do not use diagnostics test counts or seroprevalence data to demonstrate the utility of including these often unused data streams. We apply our Bayesian data integration method to COVID-19 surveillance data collected in Orange County, California between March 2020 and February 2021 and find that 32--72\% of the Orange County residents experienced SARS-CoV-2 infection by mid-January, 2021. Despite this high number of infections, our results suggest that the abrupt end of the winter surge in January 2021 was due to both behavioral changes and a high level of accumulated natural immunity.

The use of superconducting microresonators together with quantum-limited Josephson parametric amplifiers has enhanced the sensitivity of pulsed electron spin resonance (ESR) measurements by more than four orders of magnitude. So far, the microwave resonators and amplifiers have been designed as separate components due to the incompatibility of Josephson junction-based devices with magnetic fields. This has produced complex spectrometers and raised technical barriers toward adoption of the technique. Here, we circumvent this issue by coupling an ensemble of spins directly to a weakly nonlinear and magnetic field-resilient superconducting microwave resonator. We perform pulsed ESR measurements with a 1-pL mode volume containing 6 × 107 spins and amplify the resulting signals within the device. When considering only those spins that contribute to the detected signals, we find a sensitivity of [Formula: see text] for a Hahn echo sequence at a temperature of 400 mK. In situ amplification is demonstrated at fields up to 254 mT, highlighting the technique's potential for application under conventional ESR operating conditions.

Health care among forcibly displaced persons is frequently driven by siloed approaches. Aspects of the built environment, social factors, and the bidirectional relationship between the changing ecosystem and residents are often ignored in health policy design and implementation. While recognizing factors that create a preference for siloed approaches and appreciating the work of humanitarian agencies, we argue for a new data-driven and holistic approach to understand the health of the forcibly displaced. It should be rooted in the realities of the emergence of new diseases, dynamic demographics, and degrading environments around the displaced communities. Such an approach envisions refugee and internally displaced camps as dynamic, complex ecosystems that alter, and are altered by, spatial and temporal factors. At the root of this approach is the necessity to work across disciplines, to think holistically, to go beyond treating single ailments, and to develop ethical approaches that provide dignity to those who are forcibly displaced.

Aedes mosquitoes are some of the most important and globally expansive vectors of disease. Public health efforts are largely focused on prevention of human-vector contact. A range of entomological indices are used to measure risk of disease, though with conflicting results (i.e. larval or adult abundance does not always predict risk of disease). There is a growing interest in the development and use of biomarkers for exposure to mosquito saliva, including for Aedes spp, as a proxy for disease risk. In this study, we conduct a comprehensive geostatistical analysis of exposure to Aedes mosquito bites among a pediatric cohort in a peri‑urban setting endemic to dengue, Zika, and chikungunya viruses. We use demographic, household, and environmental variables (the flooding index (NFI), land type, and proximity to a river) in a Bayesian geostatistical model to predict areas of exposure to Aedes aegypti bites. We found that hotspots of exposure to Ae. aegypti salivary gland extract (SGE) were relatively small (< 500 m and sometimes < 250 m) and stable across the two-year study period. Age was negatively associated with antibody responses to Ae. aegypti SGE. Those living in agricultural settings had lower antibody responses than those living in urban settings, whereas those living near recent surface water accumulation were more likely to have higher antibody responses. Finally, we incorporated measures of larval and adult density in our geostatistical models and found that they did not show associations with antibody responses to Ae. aegypti SGE after controlling for other covariates in the model. Our results indicate that targeted house- or neighborhood-focused interventions may be appropriate for vector control in this setting. Further, demographic and environmental factors more capably predicted exposure to Ae. aegypti mosquitoes than commonly used entomological indices.

Mass drug administration (MDA) with antimalarials has been shown to reduce prevalence and interrupt transmission in small populations, in populations with reliable access to antimalarial drugs, and in populations where sustained improvements in diagnosis and treatment are possible. In addition, when MDA is effective it eliminates both drug-resistant parasites and drug-sensitive parasites, which has the long-term benefit of extending the useful therapeutic life of first-line therapies for all populations, not just the focal population where MDA was carried out. However, in order to plan elimination measures effectively, it is necessary to characterize the conditions under which failed MDA could exacerbate resistance. We use an individual-based stochastic model of Plasmodium falciparum transmission to evaluate this risk for MDA using dihydroartemisinin-piperaquine (DHA-PPQ), in populations where access to antimalarial treatments may not be uniformly high and where re-importation of drug-resistant parasites may be common. We find that artemisinin-resistance evolution at the kelch13 locus can be accelerated by MDA when all three of the following conditions are met: (1) strong genetic bottlenecking that falls short of elimination, (2) re-importation of artemisinin-resistant genotypes, and (3) continued selection pressure during routine case management post-MDA. Accelerated resistance levels are not immediate but follow the rebound of malaria cases post-MDA, if this is allowed to occur. Crucially, resistance is driven by the selection pressure during routine case management post-MDA and not the selection pressure exerted during the MDA itself. Second, we find that increasing treatment coverage post-MDA increases the probability of local elimination in low-transmission regions (prevalence < 2%) in scenarios with both low and high levels of drug-resistance importation. This emphasizes the importance of planning for and supporting high coverage of diagnosis and treatment post-MDA.

Targeted mass primaquine treatment (TPT) might be an effective intervention to facilitate elimination of vivax malaria in Myanmar by 2030. In this study, we explored the factors hindering coverage of a TPT campaign conducted in a malarious township of northern Myanmar. From August 2019 to July 2020, a cross-sectional exploratory design including quantitative and qualitative data was conducted in five villages with high P. vivax prevalence following a TPT campaign. Among a targeted population of 2322; 1973 (85.0%) participated in the baseline mass blood survey (MBS) and only 52.0% of the total targeted population (1208, 91.9% of total eligible population) completed the TPT. G6PD deficiency was found among 13.5% of total MBS participants and those were excluded from TPT. Of 1315 eligible samples, farmers and gold miners, males, and those aged 15 to 45 years had higher percentages of non-participation in TPT. Qualitative findings showed that most of the non-participation groups were outside the villages during TPT because of time-sensitive agricultural and other occupational or education-related purposes. In addition to mitigating of some inclusion criteria (i.e. including young children or offering weekly PQ treatment to G6PD deficient individuals), strengthening community awareness and increasing engagement should be pursued to increase community participation.

BackgroundDespite notable progress in the control and prevention of malaria in the Horn of Africa, the disease continues to cause significant morbidity and mortality in various regions of Ethiopia, and elsewhere in the region. The transmission of malaria is affected by genetic, sociocultural, and ecological factors. Lare is an Ethiopian district adjacent to the Ethio-South Sudan border, in Gambella region. The region currently has the highest prevalence of malaria in Ethiopia. This study assesses the burden and spatiotemporal patterns of disease transmission, including the effect of climatic factors on the occurrence of malaria, across an international border crossing. This understanding can assist in crafting informed programmatic and policy decisions for interventions.MethodsThis study was conducted in Lare district, Southwest Ethiopia, a temperate zone. A retrospective descriptive analysis was conducted using clinical service data collected between 2011 and 2021 from the 9 health facilities of the district. Both clinically diagnosed patients and those identified using microscopy and rapid diagnostic testing (RDT) were included in the study. Additionally, climate data was incorporated into analyses. Examples of analyses include malaria burden, positivity rate, incidence, species frequency, and an ANOVA to assess inter-annual case number and meteorological factor variation.ResultsBetween 2011 and 2021, a total of 96,616 suspected malaria cases were tested by microscopy or RDT, and 39,428 (40.8%) of these cases were reported as positive. There were 1276 patients admitted with 22 deaths recorded. There were further more significant fluctuations in positivity rates across years, the highest being 74.5% in 2021. Incidence varied from 18.0% in 2011 to 151.6% in 2016. The malaria parasite species most detected was Plasmodium falciparum, followed by a smaller proportion of Plasmodium vivax. The greatest proportions of P. falciparum cases were observed in 2018 and 2019, at 97.4% and 97.0% prevalence, respectively. There was significant seasonal variation in case number, the highest observed in July through September of each year. Climatic conditions of annual rainfall, temperature and humidity favored the increment of malaria cases from June until October.ConclusionThe study shows that the burden, i.e. morbidity and mortality (with fluctuating patterns) of malaria are still significant public health problems and can pose serious consequences in the district. This has implication for cross-border malaria transmission risk due to considerable border crossings. The predominant cause of the disease is P. falciparum, which causes severe complications in patients. The district has to prepare to deal with such complications for better patient care and outcomes.

BackgroundMyanmar bears the heaviest malaria burden in the Greater Mekong Subregion (GMS). This study assessed the spatio-temporal dynamics and environmental predictors of Plasmodium falciparum and Plasmodium vivax malaria in Myanmar.MethodsMonthly reports of malaria cases at primary health centers during 2011-2017 were analyzed to describe malaria distribution across Myanmar at the township and state/region levels by spatial autocorrelation (Moran index) and spatio-temporal clustering. Negative binomial generalized additive models identified environmental predictors for falciparum and vivax malaria, respectively.ResultsFrom 2011 to 2017, there was an apparent reduction in malaria incidence in Myanmar. Malaria incidence peaked in June each year. There were significant spatial autocorrelation and clustering with extreme spatial heterogeneity in malaria cases and test positivity across the nation (P

BackgroundMass drug administration (MDA) with primaquine (PQ) is being considered for accelerating Plasmodium vivax elimination in remaining active foci. This study aimed to determine the acceptability of MDA with PQ in malaria endemic villages in a malarious setting in the South of Thailand undergoing MDA with PQ.MethodsA cross-sectional mixed-methods approach was conducted in seven malaria endemic villages where MDA with PQ was implemented. The data were collected from community villagers and health workers using structured questionnaires, in-depth interviews, and focus group discussions. Descriptive statistics and logistic regression models were used for quantitative data analysis. Thematic analysis was applied for qualitative data.ResultsAmong a total of 469 participants from the MDA villages, 293 participants were eligible for MDA with PQ and 79.86% (234) completed 14-days of PQ. The logistic regressions indicated that males (adjusted odds ratio: 2.52 [95% confidence interval: 1.33-4.81]) and those who are farmers (2.57 [1.12-5.90]) were most likely to participate in the MDA. Among 293 participants in the post-MDA study, 74.06% had originally agreed to participate in the MDA with PQ while 25.94% had originally reported not wanting to participate in the MDA. Of those who originally reported being willing to participate in the MDA, 71.23% followed through with participation in the first or second round. Conversely, 93.24% of those who originally reported not being willing to participate in the MDA did in fact participate in the MDA. Factors contributing to higher odds of agreeing to participate and following through with participation included being male (1.98 [1.06-3.69]) and correctly responding that malaria is preventable (2.32 [1.01-5.35]) with some differences by village. Five key themes emerged from the qualitative analyses: concern about side effects from taking PQ; disbelief that malaria could be eliminated in this setting; low overall concern about malaria infections; misunderstandings about malaria; and a general need to tailor public health efforts for this unique context.ConclusionWhile the reported likelihood of participating in MDA was high in this setting, actual follow-through was relatively moderate, partially because of eligibility (roughly 71% of those in the follow-up survey who originally agreed to participate actually followed through with participation). One of the largest concerns among study participants was PQ-related side effects-and these concerns likely heavily influenced participant adherence to the MDA. The results of this study can be used to tailor future MDAs, or other public health interventions, in this and potentially other similar settings.

BackgroundThe collection and utilization of surveillance data is essential in monitoring progress towards achieving malaria elimination, in the timely response to increases in malaria case numbers and in the assessment of programme functioning. This paper describes the surveillance activities used by the malaria elimination task force (METF) programme which operates in eastern Myanmar, and provides an analysis of data collected from weekly surveillance, case investigations, and monitoring and evaluation of programme performance.MethodsThis retrospective analysis was conducted using data collected from a network of 1250 malaria posts operational between 2014 and 2021. To investigate changes in data completeness, malaria post performance, malaria case numbers, and the demographic details of malaria cases, summary statistics were used to compare data collected over space and time.ResultsIn the first 3 years of the METF programme, improvements in data transmission routes resulted in a 18.9% reduction in late reporting, allowing for near real-time analysis of data collected at the malaria posts. In 2020, travel restrictions were in place across Karen State in response to COVID-19, and from February 2021 the military coup in Myanmar resulted in widescale population displacement. However, over that period there has been no decline in malaria post attendance, and the majority of consultations continue to occur within 48 h of fever onset. Case investigations found that 43.8% of cases travelled away from their resident village in the 3 weeks prior to diagnosis and 36.3% reported never using a bed net whilst sleeping in their resident village, which increased to 72.2% when sleeping away from their resident village. Malaria post assessments performed in 82.3% of the METF malaria posts found malaria posts generally performed to a high standard.ConclusionsSurveillance data collected by the METF programme demonstrate that despite significant changes in the context in which the programme operates, malaria posts have remained accessible and continue to provide early diagnosis and treatment contributing to an 89.3% decrease in Plasmodium falciparum incidence between 2014 and 2021.

BackgroundLand use change has increasingly been expanding throughout the world in the past decades. It can have profound effects on the spatial and temporal distribution of vector borne diseases like malaria through ecological and habitat change. Understanding malaria disease occurrence and the impact of prevention interventions under this intense environmental modification is important for effective and efficient malaria control strategy.MethodsA descriptive ecological study was conducted by reviewing health service records at Abobo district health office. The records were reviewed to extract data on malaria morbidity, mortality, and prevention and control methods. Moreover, Meteorological data were obtained from Gambella region Meteorology Service Center and National Meteorology Authority head office. Univariate, bivariate and multivariate analysis techniques were used to analyze the data.ResultsFor the twelve-year time period, the mean annual total malaria case count in the district was 7369.58. The peak monthly malaria incidence was about 57 cases per 1000 people. Only in 2009 and 2015 that zero death due to malaria was recorded over the past 12 years. Fluctuating pattern of impatient malaria cases occurrence was seen over the past twelve years with an average number of 225.5 inpatient cases. The data showed that there is a high burden of malaria in the district. Plasmodium falciparum (Pf) was a predominant parasite species in the district with the maximum percentage of about 90. There was no statistically significant association between season and total malaria case number (F3,8: 1.982, P:0.195). However, the inter-annual total case count difference was statistically significant (F11,132: 36.305, p

BackgroundHuman mobility behaviour modelling plays an essential role in the understanding and control of the spread of contagious diseases by limiting the contact among individuals, predicting the spatio-temporal evolution of an epidemic and inferring migration patterns. It informs programmatic and policy decisions for effective and efficient intervention. The objective of this research is to assess the human mobility pattern and analyse its implication for malaria disease epidemiology.MethodsIn this study, human mobility patterns in Benishangul-Gumuz and Gambella regions in Western Ethiopia were explored based on a cellular network mobility parameter (e.g., handover rate) via real world data. Anonymized data were retrieved for mobile active users with mobility related information. The data came from anonymous traffic records collected from all the study areas. For each cell, the necessary mobility parameter data per hour, week and month were collected. A scale factor was computed to change the mobility parameter value to the human mobility pattern. Finally, the relative human mobility probability for each scenario was estimated. MapInfo and Matlab softwares were used for visualization and analysis purposes. Hourly travel patterns in the study settings were compared with hourly malaria mosquito vector feeding behaviour.ResultsHeterogeneous human movement patterns were observed in the two regions with some areas showing typically high human mobility. Furthermore, the number of people entering into the two study regions was high during the highest malaria transmission season. Two peaks of hourly human movement, 8:00 to 9:00 and 16:00 to 18:00, emerged in Benishangul-Gumuz region while 8:00 to 10:00 and 16:00 to 18:00 were the peak hourly human mobility time periods in Gambella region. The high human movement in the night especially before midnight in the two regions may increase the risk of getting mosquito bite particularly by early biters depending on malaria linked human behaviour of the population.ConclusionsHigh human mobility was observed both within and outside the two regions. The population influx and efflux in these two regions is considerably high. This may specifically challenge the transition from malaria control to elimination. The daily mobility pattern is worth considering in the context of malaria transmission. In line with this malaria related behavioural patterns of humans need to be properly addressed.

BackgroundWe established the first prospective cohort to understand how infection with dengue virus is influenced by vector-specific determinants such as humoral immunity to Aedes aegypti salivary proteins.MethodsChildren aged 2-9 years were enrolled in the PAGODAS (Pediatric Assessment Group of Dengue and Aedes Saliva) cohort with informed consent by their guardians. Children were followed semi-annually for antibodies to dengue and to proteins in Ae. aegypti salivary gland homogenate using enzyme-linked immunosorbent assays and dengue-specific neutralization titers. Children presented with fever at any time for dengue testing.ResultsFrom 13 July to 30 August 2018, we enrolled 771 children. At baseline, 22% (173/770) had evidence of neutralizing antibodies to 1 or more dengue serotypes. By April 2020, 51 children had symptomatic dengue while 148 dengue-naive children had inapparent dengue defined by neutralization assays. In a multivariate model, individuals with higher antibodies to Ae. aegypti salivary proteins were 1.5 times more likely to have dengue infection (hazard ratio [HR], 1.47 [95% confidence interval {CI}, 1.05-2.06]; P = .02), particularly individuals with inapparent dengue (HR, 1.64 [95% CI, 1.12-2.41]; P = .01).ConclusionsHigh levels of seropositivity to Ae. aegypti salivary proteins are associated with future development of dengue infection, primarily inapparent, in dengue-naive Cambodian children.Clinical trials registrationNCT03534245.

In the course of malaria elimination in the Greater Mekong Subregion (GMS), malaria epidemiology has experienced drastic spatiotemporal changes with residual transmission concentrated along international borders and the rising predominance of Plasmodium vivax. The emergence of Plasmodium falciparum parasites resistant to artemisinin and partner drugs renders artemisinin-based combination therapies less effective while the potential spread of multidrug-resistant parasites elicits concern. Vector behavioral changes and insecticide resistance have reduced the effectiveness of core vector control measures. In recognition of these problems, the Southeast Asian International Center of Excellence for Malaria Research (ICEMR) has been conducting multidisciplinary research to determine how human migration, antimalarial drug resistance, vector behavior, and insecticide resistance sustain malaria transmission at international borders. These efforts allow us to comprehensively understand the ecology of border malaria transmission and develop population genomics tools to identify and track parasite introduction. In addition to employing in vivo, in vitro, and molecular approaches to monitor the emergence and spread of drug-resistant parasites, we also use genomic and genetic methods to reveal novel mechanisms of antimalarial drug resistance of parasites. We also use omics and population genetics approaches to study insecticide resistance in malaria vectors and identify changes in mosquito community structure, vectorial potential, and seasonal dynamics. Collectively, the scientific findings from the ICEMR research activities offer a systematic view of the factors sustaining residual malaria transmission and identify potential solutions to these problems to accelerate malaria elimination in the GMS.

The malaria landscape in the Greater Mekong Subregion has experienced drastic changes with the ramp-up of the control efforts, revealing formidable challenges that slowed down the progress toward malaria elimination. Problems such as border malaria and cross-border malaria introduction, multidrug resistance in Plasmodium falciparum, the persistence of Plasmodium vivax, the asymptomatic parasite reservoirs, and insecticide resistance in primary vectors require integrated strategies tailored for individual nations in the region. In recognition of these challenges and the need for research, the Southeast Asian International Center of Excellence for Malaria Research has established a network of researchers and stakeholders and conducted basic and translational research to identify existing and emerging problems and develop new countermeasures. The installation of a comprehensive disease and vector surveillance system at sentinel sites in border areas with the implementation of passive/active case detection and cross-sectional surveys allowed timely detection and management of malaria cases, provided updated knowledge for effective vector control measures, and facilitated the efficacy studies of antimalarials. Incorporating sensitive molecular diagnosis to expose the significance of asymptomatic parasite reservoirs for sustaining transmission helped establish the necessary evidence to guide targeted control to eliminate residual transmission. In addition, this program has developed point-of-care diagnostics to monitor the quality of artemisinin combination therapies, delivering the needed information to the drug regulatory authorities to take measures against falsified and substandard antimalarials. To accelerate malaria elimination, this program has actively engaged with stakeholders of all levels, fostered vertical and horizontal collaborations, and enabled the effective dissemination of research findings.

ObjectiveNorthern Syria faces a large burden of influenza-like illness (ILI) and severe acute respiratory illness (SARI). This study aimed to investigate the trends of Early Warning and Response Network (EWARN) reported ILI and SARI in northern Syria between 2016 and 2021 and the potential impact of SARS-CoV-2.MethodsWe extracted weekly EWARN data on ILI/ SARI and aggregated cases and consultations into 4-week intervals to calculate case positivity. We conducted a seasonal-trend decomposition to assess case trends in the presence of seasonal fluctuations.ResultsIt was observed that 4-week aggregates of ILI cases (n = 5,942,012), SARI cases (n = 114,939), ILI case positivity, and SARI case positivity exhibited seasonal fluctuations with peaks in the winter months. ILI and SARI cases in individuals aged ≥5 years surpassed those in individuals aged