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BackgroundCoccidioidomycosis, caused by inhalation of Coccidioides spp. spores, is an emerging infectious disease that is increasing in incidence throughout the southwestern US. The pathogen is soil-dwelling, and spore dispersal and human exposure are thought to co-occur with airborne mineral dust exposures, yet fundamental exposure-response relationships have not been conclusively estimated.ObjectivesWe estimated associations between fine mineral dust concentration and coccidioidomycosis incidence in California from 2000 to 2017 at the census tract level, spatiotemporal heterogeneity in exposure-response, and effect modification by antecedent climate conditions.MethodsWe acquired monthly census tract-level coccidioidomycosis incidence data and modeled fine mineral dust concentrations from 2000 to 2017. We fitted zero-inflated distributed-lag nonlinear models to estimate overall exposure-lag-response relationships and identified factors contributing to heterogeneity in exposure-responses. Using a random-effects meta-analysis approach, we estimated county-specific and pooled exposure-responses for cumulative exposures.ResultsWe found a positive exposure-response relationship between cumulative fine mineral dust exposure in the 1-3 months before estimated disease onset and coccidioidomycosis incidence across the study region [incidence rate ratio (IRR) for an increase from 0.1 to 1.1 μg/m3=1.60; 95% CI: 1.46, 1.74]. Positive, supralinear associations were observed between incidence and modeled fine mineral dust exposures 1 [IRR=1.13 (95% CI: 1.10, 1.17)], 2 [IRR=1.15 (95% CI: 1.09, 1.20)] and 3 [IRR=1.08 (95% CI: 1.04, 1.12)] months before estimated disease onset, with the highest exposures being particularly associated. The cumulative exposure-response relationship varied significantly by county [lowest IRR, western Tulare: 1.05 (95% CI: 0.54, 2.07); highest IRR, San Luis Obispo: 3.01 (95% CI: 2.05, 4.42)]. Season of exposure and prior wet winter were modest effect modifiers.DiscussionLagged exposures to fine mineral dust were strongly associated with coccidioidomycosis incidence in the endemic regions of California from 2000 to 2017. https://doi.org/10.1289/EHP13875.

PurposeCorneal dysmorphologies (CDs) are typically classified as either regressive degenerative corneal dystrophies (CDtrs) or defective growth and differentiation-driven corneal dysplasias (CDyps). Both eye disorders have multifactorial etiologies. While previous work has elucidated many aspects of CDs, such as presenting symptoms, epidemiology, and pathophysiology, the genetic mechanisms remain incompletely understood. The purpose of this study was to analyze phenotype data from 8,707 knockout mouse lines to identify new genes associated with the development of CDs in humans.Methods8,707 knockout mouse lines phenotyped by the International Mouse Phenotyping Consortium were queried for genes associated with statistically significant (P

Using a learning theory is key when designing simulation-based learning linked to allied health professional placements to ensure the purposeful selection of educational methods and to understand how it may assist learners in achieving desired learning outcomes. A narrative review was undertaken to identify the learning theories reported in simulation-based learning linked to allied health professional placements and how the learning outcomes aligned with the reported theories. Only eight of the 25 reviewed studies explicitly reported a learning theory, with minimal attempt to link them to the learning experience. Educators are encouraged to develop an understanding of the breadth and depth of learning theories and how they can best align these with the desired learning outcomes to allow the best fit for purpose. As a result, the authors have developed a practical guide to assist educators in designing simulation-based learning to better understand how learning theories could be incorporated and the anticipated outcomes that could be measured.

Children's use of the Internet comes with both risks and opportunities. To minimize risks and maximize opportunities, parents may choose to observe, enable, and/or restrict their children's Internet use. However, parents' high confidence in their children's online safety can itself be a risk factor inhibiting parental awareness of online risks. This research aims to test whether confident parents are accurately aware of how frequently their child has experienced risks online. To this end, construct validity and reliability of scales measuring parental self-efficacy, restrictive-enabling-observant mediation, awareness, and Internet use were established first. Next, a conceptual model of parental awareness was proposed. These results were based on a two-parameter-logistic-model of item response theory, minimum-rank factor analysis, and parallel-mediation analysis of self-reports by a convenience sample of 388 parents in Ireland (Autumn 2019). Confident parents mostly reported their child experienced no online risk in the past couple of months, whereas unconfident parents reported their child experienced an online risk once, twice, or more times. Results of the mediation analysis indicated that confident parents likely underestimated, whereas unconfident parents overestimated, how frequently their child experienced an online risk. The accuracy of parental awareness depended on their mediation strategies, particularly restrictive mediation. Further research is needed to test whether training parents on self-efficacy and mediation of children's Internet use raises their awareness of the children's online risks.

PURPOSE: To assess whether simultaneous normalization of late-night salivary cortisol (LNSC) and mean urinary free cortisol (mUFC) in patients with Cushing disease treated with osilodrostat is associated with better clinical outcomes than control of mUFC or LNSC alone. METHODS: Pooled data from two phase III osilodrostat studies (LINC 3 and LINC 4) were analyzed. Both comprised a 48-week core phase and an optional open-label extension. Changes in cardiovascular/metabolic-related parameters, physical manifestations of hypercortisolism, and quality of life (QoL) were evaluated across the following patient subgroups: both LNSC and mUFC controlled, only mUFC controlled, only LNSC controlled, and neither controlled. RESULTS: Of 160 patients included in the analysis, 85.0% had both LNSC and mUFC uncontrolled at baseline. At week 72, 48.6% of patients had both LNSC and mUFC controlled; these patients generally exhibited greater improvements in cardiovascular/metabolic-related parameters than those with only mUFC controlled or both LNSC and mUFC uncontrolled: systolic/diastolic blood pressure, -7.4%/-4.9%, -6.0%/-5.5%, and 2.3%/0.8%, respectively; fasting plasma glucose, -5.0%, -4.8%, and 1.9%; glycated hemoglobin, -5.1%, -4.8%, and -1.3%. Weight, waist circumference, and body mass index improved with control of LNSC and/or mUFC; physical manifestations of hypercortisolism generally improved regardless of LNSC/mUFC control. Patients with both LNSC and mUFC controlled or only mUFC controlled had the greatest improvement from baseline to week 72 in QoL. CONCLUSION: In osilodrostat-treated patients with Cushing disease, normalization of LNSC and mUFC led to improvements in long-term outcomes, indicating that treatment should aim for normalization of both parameters for optimal patient outcomes. CLINICAL TRIAL IDENTIFIERS: NCT02180217 (LINC 3); NCT02697734 (LINC 4).

BackgroundCoccidioidomycosis, an emerging fungal disease in the western USA, exhibits seasonal patterns that are poorly understood, including periods of strong cyclicity, aseasonal intervals, and variation in seasonal timing that have been minimally characterized, and unexplained as to their causal factors. Coccidioidomycosis incidence has increased markedly in recent years, and our limited understanding of intra- and inter-annual seasonality has hindered the identification of important drivers of disease transmission, including climate conditions. In this study, we aim to characterize coccidioidomycosis seasonality in endemic regions of California and to estimate the relationship between drought conditions and coccidioidomycosis seasonal periodicity and timing.MethodsWe analysed data on all reported incident cases of coccidioidomycosis in California from 2000 to 2021 to characterize seasonal patterns in incidence, and conducted wavelet analyses to assess the dominant periodicity, power, and timing of incidence for 17 counties with consistently high incidence rates. We assessed associations between seasonality parameters and measures of drought in California using a distributed lag nonlinear modelling framework.FindingsAll counties exhibited annual cyclicity in incidence (i.e., a dominant wavelet periodicity of 12 months), but there was considerable heterogeneity in seasonal strength and timing across regions and years. On average, 12-month periodicity was most pronounced in the Southern San Joaquin Valley and Central Coast. Further, the annual seasonal cycles in the Southern San Joaquin Valley and the Southern Inland regions occurred earlier than those in coastal and northern counties, yet the timing of annual cycles became more aligned among counties by the end of the study period. Drought conditions were associated with a strong attenuation of the annual seasonal cycle, and seasonal peaks became more pronounced in the 1-2 years after a drought ended.InterpretationWe conclude that drought conditions do not increase the risk of coccidioidomycosis onset uniformly across the year, but instead promote increased risk concentrated within a specific calendar period (September to December). The findings have important implications for public health preparedness, and for how future shifts in seasonal climate patterns and extreme events may impact spatial and temporal coccidioidomycosis risk.FundingNational Institutes of Health.

A regulated stress response is essential for healthy child growth and development trajectories. We conducted a cluster-randomized trial in rural Bangladesh (funded by the Bill & Melinda Gates Foundation, ClinicalTrials.gov NCT01590095) to assess the effects of an integrated nutritional, water, sanitation, and handwashing intervention on child health. We previously reported on the primary outcomes of the trial, linear growth and caregiver-reported diarrhea. Here, we assessed additional prespecified outcomes: physiological stress response, oxidative stress, and DNA methylation (N = 759, ages 1-2 years). Eight neighboring pregnant women were grouped into a study cluster. Eight geographically adjacent clusters were block-randomized into the control or the combined nutrition, water, sanitation, and handwashing (N + WSH) intervention group (receiving nutritional counseling and lipid-based nutrient supplements, chlorinated drinking water, upgraded sanitation, and handwashing with soap). Participants and data collectors were not masked, but analyses were masked. There were 358 children (68 clusters) in the control group and 401 children (63 clusters) in the intervention group. We measured four F2-isoprostanes isomers (iPF(2α)-III; 2,3-dinor-iPF(2α)-III; iPF(2α)-VI; 8,12-iso-iPF(2α)-VI), salivary alpha-amylase and cortisol, and methylation of the glucocorticoid receptor (NR3C1) exon 1F promoter including the NGFI-A binding site. Compared with control, the N + WSH group had lower concentrations of F2-isoprostanes isomers (differences ranging from -0.16 to -0.19 log ng/mg of creatinine, P

Objective  While postoperative cerebrospinal fluid (CSF) leak rates of pituitary tumors have been frequently studied, there are fewer studies examining postoperative CSF leak rates for extrasellar tumors. The purpose of this study was to identify risk factors for the development of postoperative CSF leak in patients undergoing endoscopic surgery for extrasellar tumors. Methods  A retrospective chart review was done for patients who underwent endoscopic resection for extrasellar tumors between 2008 and 2020. Age, gender, tumor type, tumor location, tumor size, reconstruction technique, medical comorbidities, and other potential risk factors were identified. Data was analyzed to identify significant risk factors for development of postoperative CSF leak. Results  There were 100 patients with extrasellar tumors who developed intraoperative CSF leaks. Seventeen patients (17%) developed postoperative CSF leaks. Leaks occurred at a median of 2 days following surgery (range 0-34 days). Clival tumors had a significantly higher incidence of postoperative leak than those in other sites ( p

Doctoral students' ability to understand, use, and build on theory in educational research is a critical aspect of their learning to be successful scholars. Unfortunately, there is a paucity of work that explores the voices of graduate students articulating their experiences as they learn about theory. Using Positioning Theory to frame their work, the authors of this paper examined doctoral students' evolving understandings of theory and its uses in educational research. This work has important implications for concrete ways that senior faculty can work with doctoral students to foster their understanding of theory and its uses in educational research.

'FUSE' is an anti-bullying and online safety programme developed to support schools in complying with the Action Plan Procedures (2013). Between 2019 and 2022, 56% of all Post-Primary Schools in Ireland registered for the programme. FUSE is designed to address two key concerns, (a) students tend not to report bullying, and (b) students are increasingly facing online risks. FUSE aims to increase student's self-efficacy to recognise and report bullying behaviour and online harms safely. The programme is informed by Latané and Darley's bystander intervention model which outlines five sequential steps that an individual needs to follow in order to take action. This paper reports on the implementation of FUSE in Post Primary Schools in Ireland, justifying its theoretical base and model, and conveying the results of an empirical study conducted amongst a sample of 1254 Post Primary students (14-15 years of age) in 41 schools upon completion of the programme. Upon completion of the programme students reported high levels of self-efficacy in relation to noticing, responding and willingness to report. Future research will implement a pre- and post-study design to draw firmer conclusions regarding the effectiveness of the intervention.

As genetic tools continue to emerge and mature, more information is revealed about the identity and diversity of microbial community members. Genetic tools can also be used to make predictions about the chemistry that bacteria and fungi produce to function and communicate with one another and the host. Ongoing efforts to identify these products and link genetic information to microbiome chemistry rely on analytical tools. This tutorial highlights recent advancements in microbiome studies driven by techniques in mass spectrometry.

Natural history museums are vital repositories of specimens, samples and data that inform about the natural world; this Formal Comment revisits a Perspective that advocated for the adoption of compassionate collection practices, querying whether it will ever be possible to completely do away with whole animal specimen collection.

The importance of making online and distance education successful has been dramatically prioritized due to the COVID-19 pandemic. Student retention is a key performance indicator in online higher education. Evidence suggests that within online distance education the key to retaining students is to encourage an engaging and supportive online community. Online asynchronous forums are one method that has been employed to promote such engagement. This study investigated the relationship between online forum activity and student retention amongst 21 tutor groups on an Open University Level 1 module. It found that the volume of tutor group forum activity had a significant association with student retention (p<0.05 two-tailed, Pearson r=0.53), with student contributions having a greater impact on retention (p<0.01 two-tailed, Pearson r=0.628) than tutor contributions. Although tutor contributions did not appear to impact student retention directly the number of tutor and student posts were highly correlated (p<0.001, two tailed, Pearson r=0.86). Results indicate that asynchronous forums can be an effective tool in promoting student retention in an online distance learning environment. Important factors that impact on student retention within the educational medium of asynchronous forums are evidenced. The implications of these findings for educators are discussed. [Note: The page range (103-118) shown on the PDF is incorrect. The correct page range for this article is p103-117.]

The majority of corticotroph adenomas are benign but some are locally invasive, demonstrate high rates of recurrence, and exhibit a relatively poor response to often repeated surgical, medical, and radiation treatment. Herein, we summarize the currently known somatic and genetic mutations and other molecular factors that influence the pathogenesis of these tumors and discuss currently available therapies. Although recent molecular studies have advanced our understanding of the pathogenesis and behavior of these refractory corticotroph adenomas, these insights do not reliably guide treatment choices at present. Development of additional diagnostic tools and novel tumor-directed therapies that offer efficacious treatment choices for patients with refractory corticotroph adenomas are needed.

OBJECTIVE: To evaluate the long-term efficacy and safety of osilodrostat in patients with Cushings disease. METHODS: The multicenter, 48-week, Phase III LINC 4 clinical trial had an optional extension period that was initially intended to continue to week 96. Patients could continue in the extension until a managed-access program or alternative treatment became available locally, or until a protocol amendment was approved at their site that specified that patients should come for an end-of-treatment visit within 4 weeks or by week 96, whichever occurred first. Study outcomes assessed in the extension included: mean urinary free cortisol (mUFC) response rates; changes in mUFC, serum cortisol and late-night salivary cortisol (LNSC); changes in cardiovascular and metabolic-related parameters; blood pressure, waist circumference and weight; changes in physical manifestations of Cushings disease; changes in patient-reported outcomes for health-related quality of life; changes in tumor volume; and adverse events. Results were analyzed descriptively; no formal statistical testing was performed. RESULTS: Of 60 patients who entered, 53 completed the extension, with 29 patients receiving osilodrostat for more than 96 weeks (median osilodrostat duration: 87.1 weeks). The proportion of patients with normalized mUFC observed in the core period was maintained throughout the extension. At their end-of-trial visit, 72.4% of patients had achieved normal mUFC. Substantial reductions in serum cortisol and LNSC were also observed. Improvements in most cardiovascular and metabolic-related parameters, as well as physical manifestations of Cushings disease, observed in the core period were maintained or continued to improve in the extension. Osilodrostat was generally well tolerated; the safety profile was consistent with previous reports. CONCLUSION: Osilodrostat provided long-term control of cortisol secretion that was associated with sustained improvements in clinical signs and physical manifestations of hypercortisolism. Osilodrostat is an effective long-term treatment for patients with Cushings disease. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT02180217.

The frequency and severity of wildfires in the Western United States have increased over recent decades, motivating hypotheses that wildfires contribute to the incidence of coccidioidomycosis, an emerging fungal disease in the Western United States with sharp increases in incidence observed since 2000. While coccidioidomycosis outbreaks have occurred among wildland firefighters clearing brush, it remains unknown whether fires are associated with an increased incidence among the general population.MethodsWe identified 19 wildfires occurring within California's highly endemic San Joaquin Valley between 2003 and 2015. Using geolocated surveillance records, we applied a synthetic control approach to estimate the effect of each wildfire on the incidence of coccidioidomycosis among residents that lived within a hexagonal buffer of 20 km radii surrounding the fire.ResultsWe did not detect excess cases due to wildfires in the 12 months (pooled estimated percent change in cases: 2.8%; 95% confidence interval [CI] = -29.0, 85.2), 13-24 months (7.9%; 95% CI = -27.3, 113.9), or 25-36 months (17.4%; 95% CI = -25.1, 157.1) following a wildfire. When examined individually, we detected significant increases in incidence following three of the 19 wildfires, all of which had relatively large adjacent populations, high transmission before the fire, and a burn area exceeding 5,000 acres.DiscussionWe find limited evidence that wildfires drive increases in coccidioidomycosis incidence among the general population. Nevertheless, our results raise concerns that large fires in regions with ongoing local transmission of Coccidioides may be associated with increases in incidence, underscoring the need for field studies examining Coccidioides spp. in soils and air pre- and post-wildfires.

Genome editing with CRISPR-associated (Cas) proteins holds exceptional promise for "correcting" variants causing genetic disease. To realize this promise, off-target genomic changes cannot occur during the editing process. Here, we use whole genome sequencing to compare the genomes of 50 Cas9-edited founder mice to 28 untreated control mice to assess the occurrence of S. pyogenes Cas9-induced off-target mutagenesis. Computational analysis of whole-genome sequencing data detects 26 unique sequence variants at 23 predicted off-target sites for 18/163 guides used. While computationally detected variants are identified in 30% (15/50) of Cas9 gene-edited founder animals, only 38% (10/26) of the variants in 8/15 founders validate by Sanger sequencing. In vitro assays for Cas9 off-target activity identify only two unpredicted off-target sites present in genome sequencing data. In total, only 4.9% (8/163) of guides tested have detectable off-target activity, a rate of 0.2 Cas9 off-target mutations per founder analyzed. In comparison, we observe ~1,100 unique variants in each mouse regardless of genome exposure to Cas9 indicating off-target variants comprise a small fraction of genetic heterogeneity in Cas9-edited mice. These findings will inform future design and use of Cas9-edited animal models as well as provide context for evaluating off-target potential in genetically diverse patient populations.

BackgroundMicrophthalmia, anophthalmia, and coloboma (MAC) spectrum disease encompasses a group of eye malformations which play a role in childhood visual impairment. Although the predominant cause of eye malformations is known to be heritable in nature, with 80% of cases displaying loss-of-function mutations in the ocular developmental genes OTX2 or SOX2, the genetic abnormalities underlying the remaining cases of MAC are incompletely understood. This study intended to identify the novel genes and pathways required for early eye development. Additionally, pathways involved in eye formation during embryogenesis are also incompletely understood. This study aims to identify the novel genes and pathways required for early eye development through systematic forward screening of the mammalian genome.ResultsQuery of the International Mouse Phenotyping Consortium (IMPC) database (data release 17.0, August 01, 2022) identified 74 unique knockout lines (genes) with genetically associated eye defects in mouse embryos. The vast majority of eye abnormalities were small or absent eyes, findings most relevant to MAC spectrum disease in humans. A literature search showed that 27 of the 74 lines had previously published knockout mouse models, of which only 15 had ocular defects identified in the original publications. These 12 previously published gene knockouts with no reported ocular abnormalities and the 47 unpublished knockouts with ocular abnormalities identified by the IMPC represent 59 genes not previously associated with early eye development in mice. Of these 59, we identified 19 genes with a reported human eye phenotype. Overall, mining of the IMPC data yielded 40 previously unimplicated genes linked to mammalian eye development. Bioinformatic analysis showed that several of the IMPC genes colocalized to several protein anabolic and pluripotency pathways in early eye development. Of note, our analysis suggests that the serine-glycine pathway producing glycine, a mitochondrial one-carbon donator to folate one-carbon metabolism (FOCM), is essential for eye formation.ConclusionsUsing genome-wide phenotype screening of single-gene knockout mouse lines, STRING analysis, and bioinformatic methods, this study identified genes heretofore unassociated with MAC phenotypes providing models to research novel molecular and cellular mechanisms involved in eye development. These findings have the potential to hasten the diagnosis and treatment of this congenital blinding disease.

BackgroundFK506 binding protein 51 (FKBP5) is a co-chaperone regulator of the glucocorticoid receptor (GR). Recent studies have reported increased FKBP5 mRNA in the circulation from patients with Cushing disease (CD) which returned to comparable levels seen in healthy controls following successful trans-nasal trans-sphenoidal (TNTS) surgical corticotroph tumor removal. However, the expression of circulating FKBP5 mRNA levels in other pituitary tumor subtypes and its specificity to corticotroph tumors is unknown.MethodsPre-operative blood was collected from consecutive patients undergoing TNTS for pituitary tumors (n = 57) at our center between 2015 and 2019. Total RNA was isolated from whole blood using RiboPure blood RNA isolation kit and real-time qPCR was used to quantitate circulating FKBP5 mRNA expression.ResultsConsistent with the prior report, higher circulating FKBP5 mRNA levels were observed in 20 patients with CD prior to surgical tumor removal, compared to 21 healthy controls (p

OBJECTIVE: This extended evaluation (EE) of the SONICS study assessed the effects of levoketoconazole for an additional 6 months following open-label, 6-month maintenance treatment in endogenous Cushings syndrome. DESIGN/METHODS: SONICS included dose-titration (150-600 mg BID), 6-month maintenance, and 6-month EE phases. Exploratory efficacy assessments were performed at months 9 and 12 (relative to the start of maintenance). For pituitary MRI in patients with Cushings disease, a threshold of ≥2 mm denoted change from baseline in the largest tumor diameter. RESULTS: Sixty patients entered EE at month 6; 61% (33/54 with data) exhibited normal mean urinary free cortisol (mUFC). At months 9 and 12, respectively, 55% (27/49) and 41% (18/44) of patients with data had normal mUFC. Mean fasting glucose, total and LDL-cholesterol, body weight, BMI, abdominal girth, hirsutism, CushingQoL, and Beck Depression Inventory-II scores improved from the study baseline at months 9 and 12. Forty-six patients completed month 12; four (6.7%) discontinued during EE due to adverse events. The most common adverse events in EE were arthralgia, headache, hypokalemia, and QT prolongation (6.7% each). No patient experienced alanine aminotransferase or aspartate aminotransferase >3× upper limit of normal, Fridericia-corrected QT interval >460 ms, or adrenal insufficiency during EE. Of 31 patients with tumor measurements at baseline and month 12 or follow-up, the largest tumor diameter was stable in 27 (87%) patients, decreased in one, and increased in three (largest increase 4 mm). CONCLUSION: In the first long-term levoketoconazole study, continued treatment through a 12-month maintenance period sustained the early clinical and biochemical benefits in most patients completing EE, without new adverse effects.

Objectives  The aim of this study was to identify the reasons for patient messages, phone calls, and emergency department (ED) visits prior to the first postoperative visit following discharge after endoscopic transnasal transsphenoidal (eTNTS) surgery. Design  This is a retrospective review of patients at a tertiary care academic center who underwent eTNTS for resection of a sellar region tumor between May 2020 and August 2021. Patient, tumor, and surgical characteristics were collected, along with postoperative, postdischarge, and readmission information. Regression analyses were performed to investigate risk factors associated with postdischarge phone calls, messages, ED visits, and readmissions. Main Outcome Measures  The main outcomes were the number of and reasons for phone calls, patient messages, and ED visits between hospital discharge and the first postoperative visit. We additionally determined whether these reasons were addressed in each patient's discharge instructions. Results  A total of 98 patients underwent eTNTS during the study period. The median length of hospital stay was 2 days (interquartile range [IQR]: 1-4 days), at which point most patients (82%) were provided with eTNTS-specific discharge instructions. First postoperative visit took place 9 days after discharge (IQR: 7-10 days). Within that time, 54% of patients made at least one phone call or sent at least electronic message and 17% presented to the ED. Most common reasons for call/message were nasal care, appointment scheduling, and symptom and medication questions. Conclusion  Through this work, we highlight the most common reasons for resource utilization via patient phone calls, messages, and ED visits among our cohort to better understand any shortfall or gap in the discharge process that may reduce these events.

BackgroundDrought is an understudied driver of infectious disease dynamics. Amidst the ongoing southwestern North American megadrought, California (USA) is having the driest multi-decadal period since 800 CE, exacerbated by anthropogenic warming. In this study, we aimed to examine the influence of drought on coccidioidomycosis, an emerging infectious disease in southwestern USA.MethodsWe analysed California census tract-level surveillance data from 2000 to 2020 using generalised additive models and distributed monthly lags on precipitation and temperature. We then developed an ensemble prediction algorithm of incident cases of coccidioidomycosis per census tract to estimate the counterfactual incidence that would have occurred in the absence of drought.FindingsBetween April 1, 2000, and March 31, 2020, there were 81 448 reported cases of coccidioidomycosis throughout California. An estimated 1467 excess cases of coccidioidomycosis were observed in California in the 2 years following the drought that occurred between 2007 and 2009, and an excess 2649 drought-attributable cases of coccidioidomycosis were observed in the 2 years following the drought that occurred between 2012 and 2015. These increased numbers of cases more than offset the declines in cases that occurred during drought. An IQR increase in summer temperatures was associated with 2·02 (95% CI 1·84-2·22) times higher incidence in the following autumn (September to November), and an IQR increase in precipitation in the winter was associated with 1·45 (1·36-1·55) times higher incidence in the autumn. The effect of winter precipitation was 36% (25-48) stronger when preceded by two dry, rather than average, winters. Incidence in arid counties was most sensitive to precipitation fluctuations, while incidence in wetter counties was most sensitive to temperature.InterpretationIn California, multi-year cycles of dry conditions followed by a wet winter increases transmission of coccidioidomycosis, especially in historically wetter areas. With anticipated increasing frequency of drought in southwestern USA, continued expansion of coccidioidomycosis, along with more intense seasons, is expected. Our results motivate the need for heightened precautions against coccidioidomycosis in seasons that follow major droughts.FundingNational Institutes of Health.