Anaplasma phagocytophilum in White-tailed Deer

We examined the reservoir potential of white-tailed deer for Anaplasma phagocytophilum. Results suggest that white-tailed deer harbor a variant strain not associated with human infection, but contrary to published reports, white-tailed deer are not a reservoir for strains that cause human disease. These results will affect surveillance studies of vector and reservoir populations

The burden of typhoid fever in low- and middle-income countries: A meta-regression approach.

BACKGROUND: Upcoming vaccination efforts against typhoid fever require an assessment of the baseline burden of disease in countries at risk. There are no typhoid incidence data from most low- and middle-income countries (LMICs), so model-based estimates offer insights for decision-makers in the absence of readily available data. METHODS: We developed a mixed-effects model fit to data from 32 population-based studies of typhoid incidence in 22 locations in 14 countries. We tested the contribution of economic and environmental indices for predicting typhoid incidence using a stochastic search variable selection algorithm. We performed out-of-sample validation to assess the predictive performance of the model. RESULTS: We estimated that 17.8 million cases of typhoid fever occur each year in LMICs (95% credible interval: 6.9-48.4 million). Central Africa was predicted to experience the highest incidence of typhoid, followed by select countries in Central, South, and Southeast Asia. Incidence typically peaked in the 2-4 year old age group. Models incorporating widely available economic and environmental indicators were found to describe incidence better than null models. CONCLUSIONS: Recent estimates of typhoid burden may under-estimate the number of cases and magnitude of uncertainty in typhoid incidence. Our analysis permits prediction of overall as well as age-specific incidence of typhoid fever in LMICs, and incorporates uncertainty around the model structure and estimates of the predictors. Future studies are needed to further validate and refine model predictions and better understand year-to-year variation in cases

A Bayesian approach for estimating typhoid fever incidence from large-scale facility-based passive surveillance data.

Funder: Public Health Research Programme; Id: http://dx.doi.org/10.13039/501100001921Decisions about typhoid fever prevention and control are based on estimates of typhoid incidence and their uncertainty. Lack of specific clinical diagnostic criteria, poorly sensitive diagnostic tests, and scarcity of accurate and complete datasets contribute to difficulties in calculating age-specific population-level typhoid incidence. Using data from the Strategic Typhoid Alliance across Africa and Asia program, we integrated demographic censuses, healthcare utilization surveys, facility-based surveillance, and serological surveillance from Malawi, Nepal, and Bangladesh to account for under-detection of cases. We developed a Bayesian approach that adjusts the count of reported blood-culture-positive cases for blood culture detection, blood culture collection, and healthcare seeking-and how these factors vary by age-while combining information from prior published studies. We validated the model using simulated data. The ratio of observed to adjusted incidence rates was 7.7 (95% credible interval [CrI]: 6.0-12.4) in Malawi, 14.4 (95% CrI: 9.3-24.9) in Nepal, and 7.0 (95% CrI: 5.6-9.2) in Bangladesh. The probability of blood culture collection led to the largest adjustment in Malawi, while the probability of seeking healthcare contributed the most in Nepal and Bangladesh; adjustment factors varied by age. Adjusted incidence rates were within or below the seroincidence rate limits of typhoid infection. Estimates of blood-culture-confirmed typhoid fever without these adjustments results in considerable underestimation of the true incidence of typhoid fever. Our approach allows each phase of the reporting process to be synthesized to estimate the adjusted incidence of typhoid fever while correctly characterizing uncertainty, which can inform decision-making for typhoid prevention and control

Local variations in the timing of RSV epidemics

Abstract Background Respiratory syncytial virus (RSV) is a primary cause of hospitalizations in children worldwide. The timing of seasonal RSV epidemics needs to be known in order to administer prophylaxis to high-risk infants at the appropriate time. Methods We used data from the Connecticut State Inpatient Database to identify RSV hospitalizations based on ICD-9 diagnostic codes. Harmonic regression analyses were used to evaluate RSV epidemic timing at the county level and ZIP code levels. Linear regression was used to investigate associations between the socioeconomic status of a locality and RSV epidemic timing. Results 9,740 hospitalizations coded as RSV occurred among children less than 2 years old between July 1, 1997 and June 30, 2013. The earliest ZIP code had a seasonal RSV epidemic that peaked, on average, 4.64 weeks earlier than the latest ZIP code. Earlier epidemic timing was significantly associated with demographic characteristics (higher population density and larger fraction of the population that was black). Conclusions Seasonal RSV epidemics in Connecticut occurred earlier in areas that were more urban (higher population density and larger fraction of the population that was). These findings could be used to better time the administration of prophylaxis to high-risk infants

Analysis of the Borrelia burgdorferi Cyclic-di-GMP-Binding Protein PlzA Reveals a Role in Motility and Virulence ▿

The cyclic-dimeric-GMP (c-di-GMP)-binding protein PilZ has been implicated in bacterial motility and pathogenesis. Although BB0733 (PlzA), the only PilZ domain-containing protein in Borrelia burgdorferi, was reported to bind c-di-GMP, neither its role in motility or virulence nor it's affinity for c-di-GMP has been reported. We determined that PlzA specifically binds c-di-GMP with high affinity (dissociation constant [Kd], 1.25 μM), consistent with Kd values reported for c-di-GMP-binding proteins from other bacteria. Inactivation of the monocistronically transcribed plzA resulted in an opaque/solid colony morphology, whereas the wild-type colonies were translucent. While the swimming pattern of mutant cells appeared normal, on swarm plates, mutant cells exhibited a significantly reduced swarm diameter, demonstrating a role of plzA in motility. Furthermore, the plzA mutant cells were significantly less infectious in experimental mice (as determined by 50% infectious dose [ID50]) relative to wild-type spirochetes. The mutant also had survival rates in fed ticks lower than those of the wild type. Consequently, plzA mutant cells failed to complete the mouse-tick-mouse infection cycle, indicating plzA is essential for the enzootic life cycle of B. burgdorferi. All of these defects were corrected when the mutant was complemented in cis. We propose that failure of plzA mutant cells to infect mice was due to altered motility; however, the possibility that an unidentified factor(s) contributed to interruption of the B. burgdorferi enzootic life cycle cannot yet be excluded

The cation diffusion facilitator family protein EmfA confers resistance to manganese toxicity in Brucella abortus 2308 and is an essential virulence determinant in mice

Brucella abortus is a Gram-negative bacterium that causes abortion and infertility in food animals and a chronic debilitating febrile disease in humans known as brucellosis. As with all pathogenic bacteria, the Brucella spp. require sufficient metal nutrition during the course of an infection. Host-mediated ‘metal withdrawal’ defenses actively restrict the bioavailability of metals which requires invading bacteria to employ high affinity metal acquisition systems to overcome these metal-limiting conditions. While obtaining sufficient metals during host infection is critical to the survival of these bacteria, avoiding metal toxicity is equally important. Excess accumulation of one metal relative to others can lead to protein mis-metallation when surplus metal ions outcompete other metal species for their native binding sites. To prevent metal toxicity, bacteria respond to high intracellular metal concentrations by means of metal-responsive transcriptional regulators that downregulate metal import systems, and exporters that remove excess intracellular metal. Manganese (Mn) is an essential micronutrient for Brucella strains, and the purpose of this study was to better define the cellular components that maintain Mn homeostasis and prevent Mn toxicity in these bacteria. The Mn-responsive repressor Mur downregulates the expression of mntH, the gene encoding the sole high affinity Mn importer in Brucella in response to increased intracellular levels of Mn. But phenotypic analysis of a B. abortus mur mutant suggests that Mur plays a minimal role in preventing Mn toxicity. Instead, an ortholog of the cation diffusion facilitator (CDF) type metal exporter EmfA, which prevents Mn toxicity in the close phylogenetic relative Rhizobium etli, is critical for preventing Mn toxicity in Brucella. The experimental findings of this study indicate that EmfA-mediated resistance to Mn toxicity plays a critical role in the virulence of Brucella strains, and suggests that the primary function of EmfA may be to maintain the proper intracellular balance of Mn in these bacteria during the course of infection.ECU Research and Creative Achievement Wee