Investigation of geographic disparities of diabetes-related hospitalizations in Florida using flexible spatial scan statistics: An ecological study.

BACKGROUND: Hospitalizations due to diabetes complications are potentially preventable with effective management of the condition in the outpatient setting. Diabetes-related hospitalization (DRH) rates can provide valuable information about access, utilization, and efficacy of healthcare services. However, little is known about the local geographic distribution of DRH rates in Florida. Therefore, the objectives of this study were to investigate the geographic distribution of DRH rates at the ZIP code tabulation area (ZCTA) level in Florida, identify significant local clusters of high hospitalization rates, and describe characteristics of ZCTAs within the observed spatial clusters. METHODS: Hospital discharge data from 2016 to 2019 were obtained from the Florida Agency for Health Care Administration through a Data Use Agreement with the Florida Department of Health. Raw and spatial empirical Bayes smoothed DRH rates were computed at the ZCTA level. High-rate DRH clusters were identified using Tango's flexible spatial scan statistic. Choropleth maps were used to display smoothed DRH rates and significant high-rate spatial clusters. Demographic, socioeconomic, and healthcare-related characteristics of cluster and non-cluster ZCTAs were compared using the Wilcoxon rank sum test for continuous variables and Chi-square test for categorical variables. RESULTS: There was a total of 554,133 diabetes-related hospitalizations during the study period. The statewide DRH rate was 8.5 per 1,000 person-years, but smoothed rates at the ZCTA level ranged from 0 to 101.9. A total of 24 significant high-rate spatial clusters were identified. High-rate clusters had a higher percentage of rural ZCTAs (60.9%) than non-cluster ZCTAs (41.8%). The median percent of non-Hispanic Black residents was significantly (p < 0.0001) higher in cluster ZCTAs than in non-cluster ZCTAs. Populations of cluster ZCTAs also had significantly (p < 0.0001) lower median income and educational attainment, and higher levels of unemployment and poverty compared to the rest of the state. In addition, median percent of the population with health insurance coverage and number of primary care physicians per capita were significantly (p < 0.0001) lower in cluster ZCTAs than in non-cluster ZCTAs. CONCLUSIONS: This study identified geographic disparities of DRH rates at the ZCTA level in Florida. The identification of high-rate DRH clusters provides useful information to guide resource allocation such that communities with the highest burdens are prioritized to reduce the observed disparities. Future research will investigate determinants of hospitalization rates to inform public health planning, resource allocation and interventions.

Determinants of disparities of diabetes-related hospitalization rates in Florida: a retrospective ecological study using a multiscale geographically weighted regression approach.

BACKGROUND: Early diagnosis, control of blood glucose levels and cardiovascular risk factors, and regular screening are essential to prevent or delay complications of diabetes. However, most adults with diabetes do not meet recommended targets, and some populations have disproportionately high rates of potentially preventable diabetes-related hospitalizations. Understanding the factors that contribute to geographic disparities can guide resource allocation and help ensure that future interventions are designed to meet the specific needs of these communities. Therefore, the objectives of this study were (1) to identify determinants of diabetes-related hospitalization rates at the ZIP code tabulation area (ZCTA) level in Florida, and (2) assess if the strengths of these relationships vary by geographic location and at different spatial scales. METHODS: Diabetes-related hospitalization (DRH) rates were computed at the ZCTA level using data from 2016 to 2019. A global ordinary least squares regression model was fit to identify socioeconomic, demographic, healthcare-related, and built environment characteristics associated with log-transformed DRH rates. A multiscale geographically weighted regression (MGWR) model was then fit to investigate and describe spatial heterogeneity of regression coefficients. RESULTS: Populations of ZCTAs with high rates of diabetes-related hospitalizations tended to have higher proportions of older adults (p < 0.0001) and non-Hispanic Black residents (p = 0.003). In addition, DRH rates were associated with higher levels of unemployment (p = 0.001), uninsurance (p < 0.0001), and lack of access to a vehicle (p = 0.002). Population density and median household income had significant (p < 0.0001) negative associations with DRH rates. Non-stationary variables exhibited spatial heterogeneity at local (percent non-Hispanic Black, educational attainment), regional (age composition, unemployment, health insurance coverage), and statewide scales (population density, income, vehicle access). CONCLUSIONS: The findings of this study underscore the importance of socioeconomic resources and rurality in shaping population health. Understanding the spatial context of the observed relationships provides valuable insights to guide needs-based, locally-focused health planning to reduce disparities in the burden of potentially avoidable hospitalizations.

Cardiac Involvement in Neurosarcoidosis: A Single-Center Investigation

BACKGROUND AND OBJECTIVES: Sarcoidosis is a multisystem inflammatory granulomatous disease. Among systemic sarcoidosis manifestations, cardiac or nervous system involvement can result in significant morbidity and mortality. We describe the overlapping incidence of cardiac sarcoidosis (CS) within a neurosarcoidosis (NS) cohort and determine the frequency of other nonsarcoid cardiac diseases in these patients. METHODS: We performed a retrospective chart review of patients evaluated at the University of Utah from 2010 to 2022. Patients were included if they had (1) at least one instance of a diagnostic code for sarcoidosis in their medical record-International Classification of Diseases (ICD) 9 code 135 or ICD 10 code D86; (2) at least one outpatient visit in the Neurology Department within the University of Utah electronic health record with a diagnosis of definite, probable, or possible NS based on 2018 consensus criteria; (3) at least one outpatient visit in the Cardiology Department within the University of Utah electronic health record; and (4) ECG available in their medical record for review. Of 64 definite, probable, or possible patients with NS in the University of Utah cohort, 52 met our inclusion criteria and were included in this study. RESULTS: Of 52 patients with NS who met our inclusion criteria, 65.38% were female, with an average age of 60.9 years (range 38-84). More than half (58%) were obese (BMI ≥ 30). CS was diagnosed in 6 patients with NS (12%). Symptoms suggestive of possible cardiac dysfunction included lower extremity edema (50%), palpitations (46%), chest pain (44%), and shortness of breath (27%). ECG abnormalities included nonspecific T-wave change (40%) and right bundle branch block (17%). Three patients experienced ventricular tachycardia: sustained in one patient and nonsustained in 2 patients. Cardiac MRI was performed in 17 patients (32.7%) and in 3 patients (17.6%), which revealed diffuse myocardial enhancement suggesting CS. DISCUSSION: In this cohort, 12% of patients with NS also had confirmed CS. In addition, these patients had a high burden of cardiovascular disease not directly attributed to sarcoidosis. Our data suggest that patients with NS require comprehensive cardiac evaluation. Future studies are needed to clarify the extent of the direct contribution of granulomatous inflammation on the cardiovascular system from the indirect contribution of treatments such as glucocorticoids that lead to increased risk of cardiovascular disease in sarcoidosis.

APOE3ch alters microglial response and suppresses Aß-induced tau seeding and spread.

A recent case report described an individual who was a homozygous carrier of the APOE3 Christchurch (APOE3ch) mutation and resistant to autosomal dominant Alzheimer's Disease (AD) caused by a PSEN1-E280A mutation. Whether APOE3ch contributed to the protective effect remains unclear. We generated a humanized APOE3ch knock-in mouse and crossed it to an amyloid-ß (Aß) plaque-depositing model. We injected AD-tau brain extract to investigate tau seeding and spreading in the presence or absence of amyloid. Similar to the case report, APOE3ch expression resulted in peripheral dyslipidemia and a marked reduction in plaque-associated tau pathology. Additionally, we observed decreased amyloid response and enhanced microglial response around plaques. We also demonstrate increased myeloid cell phagocytosis and degradation of tau aggregates linked to weaker APOE3ch binding to heparin sulfate proteoglycans. APOE3ch influences the microglial response to Aß plaques, which suppresses Aß-induced tau seeding and spreading. The results reveal new possibilities to target Aß-induced tauopathy.

Investigation of predictors of severity of diabetes complications among hospitalized patients with diabetes in Florida, 2016-2019.

BACKGROUND: Severe diabetes complications impact the quality of life of patients and may lead to premature deaths. However, these complications are preventable through proper glycemic control and management of risk factors. Understanding the risk factors of complications is important in guiding efforts to manage diabetes and reduce risks of its complications. Therefore, the objective of this study was to identify risk factors of severe diabetes complications among adult hospitalized patients with diabetes in Florida. METHODS: Hospital discharge data from 2016 to 2019 were obtained from the Florida Agency for Health Care Administration through a Data Use Agreement with the Florida Department of Health. Adapted Diabetes Complications Severity Index (aDCSI) scores were computed for 1,061,140 unique adult patients with a diagnosis of diabetes. Severe complications were defined as those with an aDCSI ≥ 4. Population average models, estimated using generalized estimating equations, were used to identify individual- and area-level predictors of severe diabetes complications. RESULTS: Non-Hispanic Black patients had the highest odds of severe diabetes complications compared to non-Hispanic White patients among both males (Odds Ratio [OR] = 1.20, 95% Confidence Interval [CI]: 1.17, 1.23) and females (OR = 1.27, 95% CI: 1.23, 1.31). Comorbidities associated with higher odds of severe complications included hypertension (OR = 2.30, 95% CI: 2.23, 2.37), hyperlipidemia (OR = 1.29, 95% CI: 1.27, 1.31), obesity (OR = 1.24, 95% CI: 1.21, 1.26) and depression (OR = 1.09, 95% CI: 1.07, 1.11), while the odds were lower for patients with a diagnosis of arthritis (OR = 0.81, 95% CI: 0.79, 0.82). Type of health insurance coverage was associated with the severity of diabetes complications, with significantly higher odds of severe complications among Medicare (OR = 1.85, 95% CI: 1.80, 1.90) and Medicaid (OR = 1.83, 95% CI: 1.77, 1.90) patients compared to those with private insurance. Residing within the least socioeconomically deprived ZIP code tabulation areas (ZCTAs) in the state had a protective effect compared to residing outside of these areas. CONCLUSIONS: Racial, ethnic, and socioeconomic disparities in the severity of diabetes complications exist among hospitalized patients in Florida. The observed disparities likely reflect challenges to maintaining glycemic control and managing cardiovascular risk factors, particularly for patients with multiple chronic conditions. Interventions to improve diabetes management should focus on populations with disproportionately high burdens of severe complications to improve quality of life and decrease premature mortality among adult patients with diabetes in Florida.

No evidence for direct thermal carryover effects on starvation tolerance in the obligate blood-feeder, Glossina morsitans morsitans.

Thermal stress during development can prime animals to cope better with similar conditions in later life. Alternatively, negative effects of thermal stress can persist across life stages and result in poorer quality adults (negative carryover effects). As mean temperatures increase due to climate change, evidence for such effects across diverse taxa is required. Using Glossina morsitans morsitans, a species of tsetse fly and vector of trypanosomiasis, we asked whether (i) adaptive developmental plasticity allows flies to survive for longer under food deprivation when pupal and adult temperatures are matched; or (ii) temperature stress during development persists into adulthood, resulting in a greater risk of death. We did not find any advantage of matched pupal and adult temperature in terms of improved starvation tolerance, and no direct negative carryover effects were observed. There was some evidence for indirect carryover effects-high pupal temperature produced flies of lower body mass, which, in turn, resulted in greater starvation risk. However, adult temperature had the largest impact on starvation tolerance by far: flies died 60% faster at 31°C than those experiencing 25°C, consequently reducing survival time from a median of 8 (interquartile range (IQR) 7-9) to 5 (IQR 5-5.25) days. This highlights differences in temperature sensitivity between life stages, as there was no direct effect of pupal temperature on starvation tolerance. Therefore, for some regions of sub-Saharan Africa, climate change may result in a higher mortality rate in emerging tsetse while they search for their first blood meal. This study reinforces existing evidence that responses to temperature are life stage specific and that plasticity may have limited capacity to buffer the effects of climate change.

Mechanistic modelling of within-mosquito viral dynamics: Insights into infection and dissemination patterns.

Vector or host competence can be defined as the ability of an individual to become infected and subsequently transmit a pathogen. Assays to measure competence play a key part in the assessment of the factors affecting mosquito-borne virus transmission and of potential pathogen-blocking control tools for these viruses. For mosquitoes, competence for arboviruses can be measured experimentally and results are usually analysed using standard statistical approaches. Here we develop a mechanistic approach to studying within-mosquito virus dynamics that occur during vector competence experiments. We begin by developing a deterministic model of virus replication in the mosquito midgut and subsequent escape and replication in the hemocoel. We then extend this to a stochastic model to capture the between-individual variation observed in vector competence experiments. We show that the dose-response of the probability of mosquito midgut infection and variation in the dissemination rate can be explained by stochastic processes generated from a small founding population of virions, caused by a relatively low rate of virion infection of susceptible cells. We also show that comparing treatments or species in competence experiments by fitting mechanistic models could provide further insight into potential differences. Generally, our work adds to the growing body of literature emphasizing the importance of intrinsic stochasticity in biological systems.

Knockdown resistance allele L1014F introduced by CRISPR/Cas9 is not associated with altered vector competence of Anopheles gambiae for o'nyong nyong virus.

Knockdown resistance (kdr) alleles conferring resistance to pyrethroid insecticides are widespread amongst vector populations. Previous research has suggested that these alleles are associated with changes in the vector competence of mosquitoes for arboviruses and Plasmodium, however non-target genetic differences between mosquito strains may have had a confounding effect. Here, to minimise genetic differences, the laboratory Anopheles gambiae Kisumu strain was compared to a CRISPR/Cas9 homozygous kdr L1014F mutant Kisumu-kdr line in order to examine associations with vector competence for o'nyong nyong virus (ONNV). Mosquitoes were infected using either blood feeds or intrathoracic microinjections. There were no significant differences in the prevalence of virus in mosquito body parts between kdr mutant and wildtype lines from either oral or intrathoracic injection routes. The ONNV titre was significantly higher in the legs of the wildtype strain at 7dpi following intrathoracic microinjection, but no other significant differences in viral titre were detected. ONNV was not detected in the saliva of mosquitoes from either strain. Our findings from per os infections suggest that the kdr L1014F allele is not associated with altered infection prevalence for ONNV, a key component of vector competence.

A retrospective investigation of spatial clusters and determinants of diabetes prevalence: scan statistics and geographically weighted regression modeling approaches.

Background: Diabetes and its complications represent a significant public health burden in the United States. Some communities have disproportionately high risks of the disease. Identification of these disparities is critical for guiding policy and control efforts to reduce/eliminate the inequities and improve population health. Thus, the objectives of this study were to investigate geographic high-prevalence clusters, temporal changes, and predictors of diabetes prevalence in Florida. Methods: Behavioral Risk Factor Surveillance System data for 2013 and 2016 were provided by the Florida Department of Health. Tests for equality of proportions were used to identify counties with significant changes in the prevalence of diabetes between 2013 and 2016. The Simes method was used to adjust for multiple comparisons. Significant spatial clusters of counties with high diabetes prevalence were identified using Tango's flexible spatial scan statistic. A global multivariable regression model was fit to identify predictors of diabetes prevalence. A geographically weighted regression model was fit to assess for spatial non-stationarity of the regression coefficients and fit a local model. Results: There was a small but significant increase in the prevalence of diabetes in Florida (10.1% in 2013 to 10.4% in 2016), and statistically significant increases in prevalence occurred in 61% (41/67) of counties in the state. Significant, high-prevalence clusters of diabetes were identified. Counties with a high burden of the condition tended to have high proportions of the population that were non-Hispanic Black, had limited access to healthy foods, were unemployed, physically inactive, and had arthritis. Significant non-stationarity of regression coefficients was observed for the following variables: proportion of the population physically inactive, proportion with limited access to healthy foods, proportion unemployed, and proportion with arthritis. However, density of fitness and recreational facilities had a confounding effect on the association between diabetes prevalence and levels of unemployment, physical inactivity, and arthritis. Inclusion of this variable decreased the strength of these relationships in the global model, and reduced the number of counties with statistically significant associations in the local model. Conclusions: The persistent geographic disparities of diabetes prevalence and temporal increases identified in this study are concerning. There is evidence that the impacts of the determinants on diabetes risk vary by geographical location. This implies that a one-size-fits-all approach to disease control/prevention would be inadequate to curb the problem. Therefore, health programs will need to use evidence-based approaches to guide health programs and resource allocation to reduce disparities and improve population health.

An epidemiological study of the predictors of multidrug resistance and methicillin resistance among Staphylococcus spp. isolated from canine specimens submitted to a diagnostic laboratory in Tennessee, USA.

Background: Understanding drivers of multidrug resistance (MDR) and methicillin resistance, which have increased among canine staphylococcal isolates, is essential for guiding antimicrobial use practices. Therefore, the objective of this study was to identify predictors of MDR and methicillin resistance among Staphylococcus spp. commonly isolated from canine clinical specimens. Methods: This retrospective study used records of canine specimens submitted to the University of Tennessee College of Veterinary Medicine Clinical Bacteriology Laboratory for bacterial culture and antimicrobial susceptibility testing between 2006 and 2017. Records from 7,805 specimens positive for the following Staphylococcus species were included for analysis: Staphylococcus pseudintermedius, Staphylococcus aureus, Staphylococcus coagulans (formerly Staphylococcus schleiferi subspecies coagulans), and Staphylococcus schleiferi (formerly S. schleiferi subsp. schleiferi). Generalized linear regression models were fit using generalized estimating equations (GEE) to identify predictors of MDR (defined as resistance to three or more antimicrobial classes) and methicillin resistance among these isolates. Results: Multidrug resistance (42.1%) and methicillin resistance (31.8%) were relatively common. Isolates from skeletal (joint and bone) specimens had the highest levels of MDR (51.3%) and methicillin resistance (43.6%), followed by cutaneous specimens (45.8% multidrug-resistant, 37.1% methicillin resistant). Staphylococcus species, specimen site, and clinical setting were significant (p < 0.01) predictors of both outcomes. Compared to S. pseudintermedius, S. schleiferi had higher odds of methicillin resistance, while S. coagulans and S. schleiferi had lower odds of MDR. The odds of both MDR and methicillin resistance for isolates from hospital patient specimens were significantly higher than those from referral patients for urine/bladder and otic specimens. Odds of MDR among isolates from skeletal specimens of hospital patients were also higher than those of referral patients. Conclusions: Staphylococcus isolates in this study had substantial levels of MDR and methicillin resistance. Differences in the odds of these outcomes between referral and hospital patient isolates did not persist for all specimen sites, which may reflect differences in diagnostic testing and antimicrobial use practices with respect to body site or system. Judicious antimicrobial use, informed by culture and susceptibility testing, is important to limit treatment failures and curb selection pressure.

Aedes albopictus invasion across Africa: the time is now for cross-country collaboration and control.

The distribution of Aedes albopictus across west Africa is well documented. However, little has been done to synthesise data and establish the current distribution of this invasive vector in central and east Africa. In this Viewpoint, we show that A albopictus is establishing across Africa, how this is potentially related to urbanisation, and how establishment poses risks of near-term increases in arbovirus transmission. We then use existing species distribution maps for A albopictus and Aedes aegypti to produce consensus estimates of suitability and make these estimates accessible. Although urban development and increased trade have economic and other societal gains, the resulting potential changes in Aedes-borne virus epidemiology require a discussion of how cross-country collaboration and mitigation could be facilitated. Failure to respond to species invasion could result in increased transmission of Aedes-associated pathogens, including dengue, chikungunya, and Rift Valley fever viruses.

Antimicrobial resistance among Streptococcus equi subspecies zooepidemicus and Rhodococcus equi isolated from equine specimens submitted to a diagnostic laboratory in Kentucky, USA.

Background: Surveillance of antimicrobial resistance (AMR) among veterinary pathogens is necessary to identify clinically relevant patterns of AMR and to inform antimicrobial use practices. Streptococcus equi subsp. zooepidemicus and Rhodococcus equi are bacterial pathogens of major clinical importance in horses and are frequently implicated in respiratory tract infections. The objectives of this study were to describe antimicrobial resistance patterns and identify predictors of AMR and multidrug resistance (MDR) (resistance to three or more antimicrobial classes) among equine S. zooepidemicus and R. equi isolates. Methods: Antimicrobial susceptibility data from equine specimens submitted to the University of Kentucky Veterinary Diagnostic Laboratory between 2012 and 2017 were used in the study. Temporal trends in AMR and MDR were assessed using the Cochran-Armitage test. Logistic regression was used to identify associations between patient characteristics and the following outcomes: (a) MDR among S. zooepidemicus isolates, and (b) resistance to macrolides and ansamycins (rifampin) among R. equi isolates. Logistic regression was also used to investigate whether resistance of S. zooepidemicus and R. equi isolates to an antimicrobial class could be predicted by resistance to other drug classes. Results: The vast majority of S. zooepidemicus (99.6%) and R. equi isolates (83%) were resistant to at least one antimicrobial agent, but no significant temporal trends in AMR were observed. Approximately half (53.3%) of the S. zooepidemicus isolates were multidrug-resistant, and there was a significant (p < 0.001) increasing temporal trend of MDR among S. zooepidemicus isolates. Resistance to penicillin, which is typically recommended for treatment of suspected S. zooepidemicus infections, also increased during the study period, from 3.3% to 9.5%. Among R. equi isolates, 19.2% were resistant to one or more macrolide antibiotics, 24% were resistant to rifampin, and 15.6% were resistant to both macrolide(s) and rifampin. For both organisms, resistance to an antimicrobial class could be predicted based on resistance profiles to other drug classes. For instance, significant (p < 0.01) predictors of ß-lactam resistance among S. zooepidemicus isolates included resistance to macrolides (Odds Ratio (OR) = 14.7) and ansamycins (OR = 9.3). Resistance to phenicols (OR = 3.7) and ansamycins (OR = 19.9) were associated with higher odds of macrolide resistance among R. equi isolates. Conclusions: The increase in MDR among S. zooepidemicus isolates is concerning. The observed levels of resistance to macrolides and rifampin among R. equi are also worrisome given the limited number of antimicrobials available for treatment of this organism. The findings of this study highlight the importance of ongoing surveillance of AMR to guide treatment decisions and directions for future research.

Patterns of antimicrobial, multidrug and methicillin resistance among Staphylococcus spp. isolated from canine specimens submitted to a diagnostic laboratory in Tennessee, USA: a descriptive study.

BACKGROUND: Multidrug- and methicillin-resistant staphylococci are both veterinary and public health concerns due to their zoonotic potential. Therefore, the objective of this study was to investigate patterns of antimicrobial, multidrug, and methicillin resistance among four Staphylococcus spp. commonly isolated from canine clinical specimens submitted to the Clinical Bacteriology Laboratory at the University of Tennessee College of Veterinary Medicine (UTCVM). METHODS: Results of antimicrobial susceptibility testing and mecA polymerase chain reaction (PCR) for isolates of four common Staphylococcus spp. isolates were obtained from the Bacteriology Laboratory at the UTCVM between 01/01/2006 and 12/31/2017. Cochran-Armitage trend test was used to assess temporal trends of antimicrobial resistance (AMR), multidrug resistance (MDR), and methicillin resistance. Kappa test of agreement was used to assess agreement between the results of PCR and disk diffusion tests. RESULTS: Most of the 7805 isolates were S. pseudintermedius (6453 isolates), followed by S. coagulans (860), S. aureus (330), and S. schleiferi (162). Among S. pseudintermedius isolates, 45.5% were MDR, and 30.8% were methicillin-resistant (MRSP). There was a significant temporal increase in MRSP (p = 0.017). Chloramphenicol resistance increased among both MRSP and methicillin-susceptible (MSSP) isolates (p <  0.0001). Among S. aureus isolates, 40.9% were MDR, 37.4% were methicillin-resistant (MRSA), and the proportion of MRSA isolates increased significantly (p = 0.0480) over time. There was an increasing temporal trend in the proportion of MDR isolates among MSSP (p = 0.0022), but a decrease among MRSP (p <  0.0001) and MRSA (p = 0.0298). S. schleiferi had the highest percentage (56.9%) of methicillin-resistant isolates. Oxacillin disk diffusion was superior to cefoxitin for the detection of mecA-mediated resistance and had almost perfect agreement with mecA PCR assay for S. pseudintermedius (95.4% agreement, kappa (κ) = 0.904; p <  0.0001), S. coagulans (95.6%, κ = 0.913; p <  0.0001) and S. schleiferi (97.7%, κ = 0.945; p <  0.0001). However, cefoxitin disk diffusion was superior to oxacillin disk diffusion and had almost perfect agreement with mecA PCR assay for S. aureus (95.3%, κ = 0.834; p <  0.0001). CONCLUSIONS: The levels of resistance and increasing temporal trends are concerning. These findings have implications for treatment decisions and public health due to the zoonotic potential of staphylococci. Continued surveillance and use of antibiograms to guide clinical decisions will be critical.

Antimicrobial resistance among Enterobacteriaceae, Staphylococcus aureus, and Pseudomonas spp. isolates from clinical specimens from a hospital in Nairobi, Kenya.

BACKGROUND: Antimicrobial resistance among pathogens of public health importance is an emerging problem in sub-Saharan Africa. Unfortunately, published information on the burden and patterns of antimicrobial resistance (AMR) in this region is sparse. There is evidence that the burden and patterns of AMR vary by geography and facility. Knowledge of local epidemiology of AMR is thus important for guiding clinical decisions and mitigation strategies. Therefore, the objective of this study was to determine the burden and predictors of AMR and multidrug resistance (MDR) among bacterial pathogens isolated from specimens submitted to the diagnostic laboratory of a hospital in Nairobi, Kenya. METHODS: This retrospective study used laboratory records of 1,217 clinical specimens submitted for bacterial culture and sensitivity testing at the diagnostic laboratory of The Karen Hospital in Nairobi, Kenya between 2012 and 2016. Records from specimens positive for Enterobacteriaceae, Staphylococcus aureus, or Pseudomonas spp. isolates were included for analysis. Firth logistic models, which minimize small sample bias, were used to investigate determinants of AMR and MDR of the isolates. RESULTS: A total of 222 specimens had bacterial growth. Most Enterobacteriaceae isolates were resistant to commonly used drugs such as penicillin/ß-lactamase inhibitor combinations (91.2%) and folate pathway inhibitors (83.7%). Resistance to extended-spectrum cephalosporins was also high (52.9%). Levels of AMR and MDR for Enterobacteriaceae were 88.5% and 51%, respectively. Among S. aureus isolates, 57.1% were AMR, while 16.7% were MDR. As many as 42.1% of the Pseudomonas spp. isolates were aminoglycoside-resistant and 15% were fluoroquinolone-resistant, but none exhibited resistance to antipseudomonal carbapenems. Half of Pseudomonas spp. isolates were AMR but none were MDR. Significant predictors of MDR among Enterobacteriaceae were organism species (p = 0.002) and patient gender (p = 0.024). CONCLUSIONS: The high levels of extended-spectrum cephalosporin resistance and MDR among Enterobacteriaceae isolates are concerning. However, the relatively low levels of MDR S. aureus, and an absence of carbapenem resistance among Pseudomonas isolates, suggests that last-line drugs are still effective against S. aureus and Pseudomonas infections. These findings are relevant for guiding evidence-based treatment decisions as well as surveillance efforts and directions for future research, and contribute to the sparse literature on AMR in sub-Saharan Africa.

A cross-sectional survey to establish Theileria parva prevalence and vector control at the wildlife-livestock interface, Northern Tanzania.

East Coast fever (ECF) in cattle is caused by the protozoan parasite Theileria parva, transmitted by Rhipicephalus appendiculatus ticks. In cattle ECF is often fatal, causing annual losses >$500 million across its range. The African buffalo (Syncerus caffer) is the natural host for T. parva but the transmission dynamics between wild hosts and livestock are poorly understood. This study aimed to determine the prevalence of T. parva in cattle, in a 30 km zone adjacent to the Serengeti National Park, Tanzania where livestock and buffalo co-exist, and to ascertain how livestock keepers controlled ECF and other vector-borne diseases of cattle. A randomised cross-sectional cattle survey and questionnaire of vector control practices were conducted. Blood samples were collected from 770 cattle from 48 herds and analysed by PCR to establish T. parva prevalence. Half body tick counts were recorded on every animal. Farmers were interviewed (n = 120; including the blood sampled herds) using a standardised questionnaire to obtain data on vector control practices. Local workshops were held to discuss findings and validate results. Overall prevalence of T. parva in cattle was 5.07% (CI: 3.70-7.00%), with significantly higher prevalence in older animals. Although all farmers reported seeing ticks on their cattle, tick counts were very low with 78% cattle having none. Questionnaire analysis indicated significant acaricide use with 79% and 41% of farmers reporting spraying or dipping with cypermethrin-based insecticides, respectively. Some farmers reported very frequent spraying, as often as every four days. However, doses per animal were often insufficient. These data indicate high levels of acaricide use, which may be responsible for the low observed tick burdens and low ECF prevalence. This vector control is farmer-led and aimed at both tick- and tsetse-borne diseases of livestock. The levels of acaricide use raise concerns regarding sustainability; resistance development is a risk, particularly in ticks. Integrating vaccination as part of this community-based disease control may alleviate acaricide dependence, but increased understanding of the Theileria strains circulating in wildlife-livestock interface areas is required to establish the potential benefits of vaccination.

The evolutionary dynamics of viruses: virion release strategies, time delays and fitness minima.

Viruses exhibit a diverse array of strategies for infecting host cells and for virion release after replication. Cell exit strategies generally involve either budding from the cell membrane or killing the host cell. The conditions under which either is at a selective advantage is a key question in the evolutionary theory of viruses, with the outcome having potentially important impacts on the course of infection and pathogenicity. Although a plethora of external factors will influence the fitness of either strategy; here, we focus just on the effects of the physical properties of the system. We develop theoretical approaches to assess the effects of the time delays between initial infection and virion release. We show that the length of the delay before apoptosis is an important trait in virus evolutionary dynamics. Our results show that for a fixed time to apoptosis, intermediate delays lead to virus fitness that is lower than short times to apoptosis - leading to an apoptotic strategy - and long times to apoptosis - leading to a budding strategy at the between-cell level. At fitness minima, selection is expected to be disruptive and the potential for adaptive radiation in virus strategies is feasible. Hence, the physical properties of the system are sufficient to explain the existence of both budding and virus-induced apoptosis. The fitness functions presented here provide a formal basis for further work focusing on the evolutionary implications of trade-offs between time delays, intracellular replication and resulting mutation rates.

Effects of maternal age and stress on offspring quality in a viviparous fly.

Many organisms show signs of deterioration with age in terms of survival and reproduction. We tested whether intraspecific variation in such senescence patterns can be driven by resource availability or reproductive history. We did this by manipulating nutritional stress and age at first reproduction and measuring age-dependent reproductive output in tsetse (Glossina morsitans morsitans), a viviparous fly with high maternal allocation. Across all treatments, offspring weight followed a bell-shaped curve with maternal age. Nutritionally stressed females had a higher probability of abortion and produced offspring with lower starvation tolerance. There was no evidence of an increased rate of reproductive senescence in nutritionally stressed females, or a reduced rate due to delayed mating, as measured by patterns of abortion, offspring weight or offspring starvation tolerance. Therefore, although we found evidence of reproductive senescence in tsetse, our results did not indicate that resource allocation trade-offs or costs of reproduction increase the rate of senescence.

Changes in Rice and Livestock Production and the Potential Emergence of Japanese Encephalitis in Africa.

The known distribution of Japanese encephalitis (JE) is limited to Asia and Australasia. However, autochthonous transmission of Japanese encephalitis virus was reported in Africa for the first time in 2016. Reasons for the current geographic restriction of JE and the circumstances that may permit emergence in non-endemic areas are not well known. Here, I assess potential changes in vector breeding habitat and livestock production in Africa that are conducive to JEV transmission, using open-source data available from the Food and Agriculture Organization between 1961 and 2019. For 16 of 57 countries in Africa, there was evidence of existing, or an increase in, conditions potentially suitable for JE emergence. This comprised the area used for rice production and the predicted proportion of blood meals on pigs. Angola, where autochthonous transmission was reported, was one of these 16 countries. Studies to better quantify the role of alternative hosts, including domestic birds in transmission in endemic regions, would help to determine the potential for emergence elsewhere. In Africa, surveillance programs for arboviruses should not rule out the possibility of Japanese encephalitis virus (JEV) circulation in areas with high pig or bird density coincident with Culicine breeding habitats.

Geographic disparities, determinants, and temporal changes in the prevalence of pre-diabetes in Florida.

BACKGROUND: Left unchecked, pre-diabetes progresses to diabetes and its complications that are important health burdens in the United States. There is evidence of geographic disparities in the condition with some areas having a significantly high risks of the condition and its risk factors. Identifying these disparities, their determinants, and changes in burden are useful for guiding control programs and stopping the progression of pre-diabetes to diabetes. Therefore, the objectives of this study were to investigate geographic disparities of pre-diabetes prevalence in Florida, identify predictors of the observed spatial patterns, as well as changes in disease burden between 2013 and 2016. METHODS: The 2013 and 2016 Behavioral Risk Factor Surveillance System data were obtained from the Florida Department of Health. Counties with significant changes in the prevalence of the condition between 2013 and 2016 were identified using tests for equality of proportions adjusted for multiple comparisons using the Simes method. Flexible scan statistics were used to identify significant high prevalence geographic clusters. Multivariable regression models were used to identify determinants of county-level pre-diabetes prevalence. RESULTS: The state-wide age-adjusted prevalence of pre-diabetes increased significantly (p ≤ 0.05) from 8.0% in 2013 to 10.5% in 2016 with 72% (48/67) of the counties reporting statistically significant increases. Significant local geographic hotspots were identified. High prevalence of pre-diabetes tended to occur in counties with high proportions of non-Hispanic black population, low median household income, and low proportion of the population without health insurance coverage. CONCLUSIONS: Geographic disparities of pre-diabetes continues to exist in Florida with most counties reporting significant increases in prevalence between 2013 and 2016. These findings are critical for guiding health planning, resource allocation and intervention programs.

A multi-center case series of sarcoid optic neuropathy.

OBJECTIVE: The diagnosis of sarcoid optic neuropathy is time-sensitive, as delayed treatment risks irreversible vision loss. We sought to analyze its characteristics and outcomes. METHODS: We performed a multi-center retrospective study of sarcoid optic neuropathy among 5 USA medical centers. Inclusion criteria were: 1) clinical optic neuropathy; 2) optic nerve/sheath enhancement on neuroimaging; 3) pathological confirmation of systemic or nervous system sarcoidosis. RESULTS: Fifty-one patients were included. The median onset age of sarcoid optic neuropathy was 50 years (range, 17-70 years) and 71% were female. The median visual acuity at nadir in the most affected eye was 20/80 (range, 20/20 to no-light-perception). Thirty-four of 50 (68%) patients had radiologic evidence of other nervous system involvement and 20 (39%) patients had symptoms/signs of other cranial nerve dysfunction. Cerebrospinal fluid analysis revealed an elevated white blood cell count in 22 of 31 (71%) patients (median: 14/µL; range: 1-643/µL). Pathologic confirmation of sarcoidosis was by biopsy of systemic/pulmonary site, 34 (67%); optic nerve/sheath, 9 (18%); or other nervous system region, 8 (16%). Forty patients improved with treatment (78%), 98% receiving corticosteroids and 65% receiving steroid-sparing immunosuppressants, yet 11/46 patients (24%) had a visual acuity of 20/200 or worse at last follow-up. CONCLUSIONS: Sarcoid optic neuropathy frequently occurs with other clinical and radiologic abnormalities caused by neurosarcoidosis and diagnostic confirmation occasionally requires optic nerve/sheath biopsy. Improvement with treatment is common but most patients have some residual visual disability. Improved recognition and a more expeditious diagnosis and treatment may spare patients from permanent vision loss.