Infection burden, periodontal pathogens, and their interactive association with incident all-cause and Alzheimer's disease dementia in a large national survey.

INTRODUCTION: Relationships and interplay of an infection burden (IB) and periodontal pathogens or periodontal disease (Pd) markers with Alzheimer's disease (AD) and all-cause dementia among US adults were examined. METHODS: Less than or equal to 2997 participants from the National Health and Nutrition Survey III were linked to CMS-Medicare [≥45 years (1988-1994); ≤30 years follow-up]. RESULTS: Hepatitis C (hazard ratio = 3.33, p = 0.004) and herpes simplex virus 2 were strongly associated with greater all-cause dementia risk. Porphyromonas gingivalis and Streptococcus oralis were associated with greater AD risk at higher IB. The red-green periodontal pathogen cluster coupled with higher IB count increased the risk of all-cause dementia among minority racial groups. Pocket probing depth associated with dementia risk at lower IB in the overall sample. DISCUSSION: Select viruses and bacteria were associated with all-cause and AD dementia, while the IB interacted with Pd markers in relation to these outcomes. HIGHLIGHTS: Interplay of infection burden (IB) and periodontal disease with dementia was tested. ≤2997 participants from NHANES III were linked to Medicare. Hepatitis C and herpes simplex virus 2 strongly associated with dementia risk. Tetanus sero-positivity increased Alzheimer's disease (AD) risk. Porphyromonas gingivalis and Streptococcus oralis associated with AD at higher IB. Red-green periodontal cluster at high IB, increased dementia in racial minorities. Pocket probing depth associated with dementia risk at lower IB.

Hospital-treated infectious diseases, genetic susceptibility and risk of type 2 diabetes: A population-based longitudinal study.

BACKGROUND: The longitudinal association between infectious diseases and the risk of type 2 diabetes (T2D) remains unclear. METHODS: Based on the UK Biobank, the prospective cohort study included a total of 396,080 participants without diabetes at baseline. We determined the types and sites of infectious diseases and incident T2D using the International Classification of Diseases 10th Revision codes (ICD-10). Time-varying Cox proportional hazard model was used to assess the association. Infection burden was defined as the number of infection episodes over time and the number of co-occurring infections. Genetic risk score (GRS) for T2D consisted of 424 single nucleotide polymorphisms. RESULTS: During a median of 9.04 [IQR, 8.3-9.7] years of follow-up, hospital-treated infectious diseases were associated with a greater risk of T2D (adjusted HR [aHR] 1.54 [95 % CI 1.46-1.61]), with risk difference per 10,000 individuals equal to 154.1 [95 % CI 140.7-168.2]. The heightened risk persisted after 5 years following the index infection. Bacterial infection with sepsis had the strongest risk of T2D (aHR 2.95 [95 % CI 2.53-3.44]) among different infection types. For site-specific analysis, bloodstream infections posed the greatest risk (3.01 [95 % CI 2.60-3.48]). A dose-response association was observed between infection burden and T2D risk within each GRS tertile (p-trend <0.001). High genetic risk and infection synergistically increased the T2D risk. CONCLUSION: Infectious diseases were associated with an increased risk of subsequent T2D. The risk showed specificity according to types, sites, severity of infection and the period since infection occurred. A potential accumulative effect of infection was revealed.

Association of hospital-treated infectious diseases and infection burden with cardiovascular diseases and life expectancy.

BACKGROUND: The association of a broad spectrum of infectious diseases with cardiovascular outcomes remains unclear. OBJECTIVES: We aim to provide the cardiovascular risk profiles associated with a wide range of infectious diseases and explore the extent to which infections reduce life expectancy. METHODS: We ascertained exposure to 900+ infectious diseases before cardiovascular disease (CVD) onset in 453,102 participants from the UK Biobank study. Time-varying Cox proportional hazard models were used. Life table was used to estimate the life expectancy of individuals aged ≥50 with different levels of infection burden (defined as the number of infection episodes over time and the number of co-occurring infections). RESULTS: Infectious diseases were associated with a greater risk of CVD events (adjusted HR [aHR] 1.79 [95% confidence interval {CI} 1.74-1.83]). For type-specific analysis, bacterial infection with sepsis had the strongest risk of CVD events [aHR 4.76 (4.35-5.20)]. For site-specific analysis, heart and circulation infections posed the greatest risk of CVD events [aHR 4.95 (95% CI 3.77-6.50)], whereas noncardiac infections also showed excess risk [1.77 (1.72-1.81)]. Synergistic interactions were observed between infections and genetic risk score. A dose-response relationship was found between infection burden and CVD risks (p-trend <0.001). Infection burden >1 led to a CVD-related life loss at age 50 by 9.3 years [95% CI 8.6-10.3]) for men and 6.6 years [5.5-7.8] for women. CONCLUSIONS: The magnitude of the infection-CVD association showed specificity in sex, pathogen type, infection burden, and infection site. High genetic risk and infection synergistically increased the CVD risk.

Burden of pulmonary tuberculosis and challenges related to tuberculosis detection in Ethiopia.

Early and rapid diagnosis of Mycobacterium tuberculosis in clinical specimen is important for the treatment of patients and control of disease transmission to the community. The disease is largely preventable and curable, but without rapid, and correct diagnostic tools for tuberculosis (TB) infection and drug resistance, it is unlikely that we can meet the national TB elimination program in Ethiopia by 2035. Moreover, drug resistant TB is becoming more common and is a great challenge for the successful control and eradication of TB. The need for rapid, accurate and affordable methods for TB management should be considered by policy makers to improve TB detection rate and reduction of TB related deaths in line with the stop TB strategy by 2030 in Ethiopia.

Cryptococcosis in Africa: What the data tell us.

Cryptococcosis is a neglected tropical disease and the main cause of fungal-related deaths in HIV-positive persons in Africa. It is an AIDS-defining illness that has almost surpassed tuberculosis (TB) in mortality despite wide coverage with antiretroviral therapy. What is known about the cryptococcosis burden in Africa is from estimations based on data from a few studies on the infection burden and associated complications. Consequently, the projected implications of cryptococcosis in Africa have been based on these estimations. This systematic review is aimed at providing unique and up-to-date data on the burden of cryptococcosis in Africa using published hospital-based research data on cryptococcosis in HIV infected and uninfected persons. The review also focused on providing temporal data on the availability of diagnostic and therapeutic options for cryptococcosis in Africa. From our results, about 40 948 cases of cryptococcosis were reported in Africa from 1969 to 2021, and the highest prevalence of cryptococcosis was from southern Africa. The most isolated species was Cryptococcus neoformans 42.4% (17 710/41 801) and only 1.3% (549/41 801) isolates were C. gattii. C. neoformans (serotype A) VN I 64.5% (918/1522) was the most prevalent serotype in Africa, while C. gattii (serotype C) VG IV was thought to pose a huge danger. However, C. neoformans (serotype A) VN I continued to be the major threat in Africa. Due to the limited availability of molecular typing methods and the widespread use of culture, direct microscopy, and serological techniques for diagnosis, 23 542 isolates were uncharacterised. Amphotericin B and flucytosine combination therapy is highly recommended for treatment of cryptococcal meningitis. However, these drugs are expensive and remain largely unavailable in most African countries. Amphotericin B requires laboratory facilities to monitor for toxicity. Although fluconazole monotherapy is the readily available treatment option for cryptococcosis, drug resistance, and high mortality have been recorded in majority of cases in Africa. The lack of awareness and paucity of published data on cryptococcosis are likely to have contributed to the underestimation of cases in Africa and led to underprioritisation of this important disease.

Cryptococcosis is a neglected tropical disease that manifests greatly in immunocompromised persons especially those with HIV infection. Our data show that managing cryptococcosis will require an integrated multidisciplinary approach that should include the utilisation of cryptococcal antigen (CrAg) testing, which is highly sensitive and cost-effective for diagnosing this disease.

Intermittent systemic exposure to lipopolysaccharide-induced inflammation disrupts hippocampal long-term potentiation and impairs cognition in aging male mice.

Age-related cognitive decline, a common component of the brain aging process, is associated with significant impairment in daily functioning and quality of life among geriatric adults. While the complexity of mechanisms underlying cognitive aging are still being elucidated, microbial exposure and the multifactorial inflammatory cascades associated with systemic infections are emerging as potential drivers of neurological senescence. The negative cognitive and neurobiological consequences of a single pathogen-associated inflammatory experience, such as that modeled through treatment with lipopolysaccharide (LPS), are well documented. Yet, the brain aging impacts of repeated, intermittent inflammatory challenges are less well studied. To extend the emerging literature assessing the impact of infection burden on cognitive function among normally aging mice, here, we repeatedly exposed adult mice to intermittent LPS challenges during the aging period. Male 10-month-old C57BL6 mice were systemically administered escalating doses of LPS once every two weeks for 2.5 months. We evaluated cognitive consequences using the non-spatial step-through inhibitory avoidance task, and both spatial working and reference memory versions of the Morris water maze. We also probed several potential mechanisms, including cortical and hippocampal cytokine/chemokine gene expression, as well as hippocampal neuronal function via extracellular field potential recordings. Though there was limited evidence for an ongoing inflammatory state in cortex and hippocampus, we observed impaired learning and memory and a disruption of hippocampal long-term potentiation. These data suggest that a history of intermittent exposure to LPS-induced inflammation is associated with subtle but significantly impaired cognition among normally aging mice. The broader impact of these findings may have important implications for standard of care involving infections in aging individuals or populations at-risk for dementia.

Predicting Potential Prevention Effects on Hospital Burden of Nosocomial Infections: A Multistate Modeling Approach.

OBJECTIVES: Hospital-acquired infections (HAIs) place a substantial burden on health systems. Tools are required to quantify the change in this burden as a result of a preventive intervention. We aim to estimate how much a reduction in the rate of hospital-acquired infections translates into a change in hospital mortality and length of stay. METHODS: Using multistate modelling and competing risks methodology, we created a tool to estimate the reduction in burden after the introduction of a preventive effect on the infection rate. The tool requires as inputs the patients' length of hospital stay, patients' infection information (status, time), patients' final outcome (discharged alive, dead), and a preventive effect. We demonstrated the methods on both simulated data and 3 published data sets from Germany, France, and Spain. RESULTS: A hypothetical prevention that cuts the infection rate in half would result in 21 lives and 2212 patient-days saved in French ventilator-associated pneumonia data, 61 lives and 3125 patient-days saved in Spanish nosocomial infection data, and 20 lives and 1585 patient-days saved in German nosocomial pneumonia data. CONCLUSIONS: Our tool provides a quick and easy means of acquiring an impression of the impact a preventive measure would have on the burden of an infection. The tool requires quantities routinely collected and computation can be done with a calculator. R code is provided for researchers to determine the burden in various settings with various effects. Furthermore, cost data can be used to get the financial benefit of the reduction in burden.

Baseline Infection Burden and Cognitive Function in Elders with Essential Tremor.

Background: Patients with essential tremor (ET) have an increased risk of cognitive impairment, yet little is known about the predictors of cognitive decline in these patients. Exposures to infectious agents throughout the lifespan may impact the later development of cognitive impairment. For example, high Infection exposure has been associated with lower cognitive performance in Alzheimer's and Parkinson's disease. However, this predictor has not been examined in ET. Objectives: To determine whether a higher baseline infection burden is associated with worse cognitive performance at baseline and greater cognitive decline over time in an ET cohort. Method/Design: 160 elderly non-demented ET participants (80.0 ± 9.5 years) underwent an extensive cognitive evaluation at three time points. At baseline, participants completed an infection burden questionnaire (t-IBQ) that elicited information on previous exposure to infectious agents and number of episodes per disease. Analysis of covariance and generalized estimated equations (GEEs) were used. Results: Overall, infection burden was not associated baseline cognitive performance. Adjusted GEE models for repeated measures yielded a significant time interaction between moderate infection burden at baseline and better performance in the attention domain over time (p = 0.013). Previous history of rubella was associated with faster rate of decline in visuospatial performance (p = 0.046). Conclusion: The data were mixed. Moderate self-reported infection burden was associated with better attention performance over time. Self-reported history of rubella infection was related to lower visuospatial performance over time in this cohort. Follow-up studies with additional design elements would be of value.

Laboratory-developed test for detection of acute Clostridium difficile infections with the capacity for quantitative sample normalization.

We describe a laboratory-developed test intended for the detection of acute Clostridium difficile infections (CDI) with the capacity for quantitative sample normalization. The test is based on the detection of the tcdB gene. However, this biomarker is also present among people without symptoms, implying that individuals with diarrhea, not caused by C. difficile may nonetheless test positive. Therefore, clinical diagnosis based on this format of testing can be challenging. In order to improve diagnostic assays capability, tcdB-based quantification methods were suggested as a potential solution, however they did not increase clinical specificity. We report methodology for a dual biomarker monitoring (total bacterial load and tcdB assay), allowing for the calculation of the relative presence of tcdB in the total bacterial population in the tested samples. We believe that this approach is clinically relevant to current assays and can improve CDI testing algorithms.

Dispersion of Echinococcus granulosus eggs from infected dogs under natural conditions in Patagonia, Argentina.

Cystic echinococcosis caused by Echinococcus granulosus is a major zoonosis of public health significance in the Patagonian region of Argentina. This investigation sought to test the hypothesis that the persistence and dispersion of the parasite eggs can be explained by physical and meteorological parameters along with final host infection and behaviour. This observational study was carried out over a five-year period within an enclosure where two dogs harbouring a worm burden ranging from 100 to 1000 mature adult E. granulosus, as well as two uninfected dogs, had previously been kept for six months. Environmental canine faeces, topsoil, pond water, and sediment samples were examined to control for the presence of eggs and coproantigens of the parasite using microscope-based techniques and copro-ELISA plus copro-Western Blot tests. The parasite eggs were detected up to 41 months later in faeces from infected dogs, soil and sediment, and coproantigen tests remained positive for up to 70 months in faeces. Overall, parasite eggs were found within a maximum distance of 115 m from the contaminated dog faeces deposition site. Our findings indicate that under Patagonian environmental conditions, egg persistence and dispersion seem to be related to the worm burden and habits of the infected dog, to prevailing wind direction and to the existence of low bushes as well as natural bodies of water. The present study is the first to provide direct evidence of interaction between bioclimatic conditions and E. granulosus egg dispersion under Patagonian field conditions.

Estimating the Burden of Serious Fungal Infections in Uruguay.

We aimed to estimate for the first time the burden of fungal infections in Uruguay. Data on population characteristics and underlying conditions were extracted from the National Statistics Institute, the World Bank, national registries, and published articles. When no data existed, risk populations were used to estimate frequencies extrapolating from the literature. Population structure (inhabitants): total 3,444,006; 73% adults; 35% women younger than 50 years. Size of populations at risk (total cases per year): HIV infected 12,000; acute myeloid leukemia 126; hematopoietic stem cell transplantation 30; solid organ transplants 134; COPD 272,006; asthma in adults 223,431; cystic fibrosis in adults 48; tuberculosis 613; lung cancer 1400. Annual incidence estimations per 100,000: invasive aspergillosis, 22.4; candidemia, 16.4; Candida peritonitis, 3.7; Pneumocystis jirovecii pneumonia, 1.62; cryptococcosis, 0.75; severe asthma with fungal sensitization, 217; allergic bronchopulmonary aspergillosis, 165; recurrent Candida vaginitis, 6323; oral candidiasis, 74.5; and esophageal candidiasis, 25.7. Although some under and overestimations could have been made, we expect that at least 127,525 people suffer from serious fungal infections each year. Sporothrichosis, histoplasmosis, paracoccidioidomycosis, and dermatophytosis are known to be frequent but no data are available to make accurate estimations. Given the magnitude of the burden of fungal infections in Uruguay, efforts should be made to improve surveillance, strengthen laboratory diagnosis, and warrant access to first line antifungals.

Infection burden in total hip and knee arthroplasties: an international registry-based perspective.

BACKGROUND: Infection remains a leading cause of failure of hip and knee replacements. Infection burden is the ratio of implants revised for infection to the total number of arthroplasties in a specific period, measuring the steady state of infection in a registry. We hypothesized infection burden would be similar among arthroplasty registries. METHODS: We evaluated publicly reported data from 6 arthroplasty registries (Australian Orthopaedic Association National Joint Replacement Registry [AOANJRR], New Zealand Joint Registry, Swedish Hip Arthroplasty Register, Swedish Knee Arthroplasty Register, National Joint Registry of England, Wales, Northern Ireland, and the Isle of Man, and the American Joint Replacement Registry) for revisions performed with an infection diagnosis over the last 6 years. RESULTS: The 2015 hip infection burden varied between registries from 0.76% (AOANJRR) to 1.24% (Swedish Hip Arthroplasty Register), and the unweighted overall average for hip infection burden was 0.97%. In 2012, 2013, and 2014, average hip infection burden held steady at 0.87%, 0.93%, and 0.94%, respectively, higher than the preceding 2 years. The 2015 knee infection burden varied from 0.88% (AOANJRR) to 1.28% (Swedish Knee Arthroplasty Register), and the unweighted average was 1.03%. In 2012, 2013, and 2014, knee infection burden was 1.04%, 1.11%, and 1.02%, respectively. These numbers were also higher than the preceding 2 years. CONCLUSIONS: Infection burden may be one measure of the overall success in registry populations as well as monitoring the steady state of infection worldwide. Despite global efforts to reduce postoperative infection, infection burden has actually increased in the selected registries over time.

Rates and burden of surgical site infections associated with pediatric colorectal surgery: insight from the National Surgery Quality Improvement Program.

PURPOSE: The purpose of this study was to characterize the rates of surgical site infections (SSI) associated with colorectal procedures in children and the relative burden of these events within the scope of pediatric surgical practice. METHODS: The NSQIP-Pediatric Public Use File was queried for all pediatric surgery procedures captured from 50 hospitals during 2012-2013. Rates of incisional and deep organ/space SSIs (ISSI and OSI, respectively) were calculated for all procedures, and the relative burden of SSIs from the entire dataset attributable to colorectal procedures was determined. RESULTS: Colorectal procedures accounted for 2.5% (2872/114,395) of the NSQIP-P caseload and contributed 7.1% of the SSI burden. The SSI rate for all colorectal procedures was 5.9% (ISSI:3.2%; OSI:2.7%), and the highest rates were associated with total abdominal colectomy (11.4%) partial colectomy (8.3%), and colostomy closure (5.0%). Inflammatory bowel disease contributed the greatest relative burden of SSIs among colorectal diagnoses (24.9%; ISSI:22%; OSI:28.6%), followed by Hirschsprung's Disease (14.2%; ISSI:15.4%; OSI:12.8%) and anorectal malformations (12.4%; ISSI:17.6%; OSI:6.4%). CONCLUSION: Colorectal procedures are responsible for a disproportionate burden of SSIs within pediatric surgery. The rate and relative burden of SSIs are particularly high for colostomy closure, partial colectomy, and procedures for inflammatory bowel disease. Efforts to reduce SSI burden may be best focused on this cohort of children.