Age, influenza pandemics and disease dynamics.

The world is currently confronting the first influenza pandemic of the 21st century [caused by a novel pandemic influenza A (H1N1) virus]. Earlier pandemics have been characterized by age distributions that are distinct from those observed with seasonal influenza epidemics, with higher attack rates (and correspondingly increased proportionate or relative mortality) in younger individuals. While the genesis of protection against infection in older individuals during a pandemic is uncertain, differential vulnerability to infection by age has important implications for disease dynamics and control, and for choice of optimal vaccination strategies. Age-related vulnerability to infection may explain differences between school- and community-derived estimates of the reproductive number (R) for a newly emerged pandemic strain, and may also help explain the failure of a newly emerged influenza A (H1N1) virus strain to cause a pandemic in 1977. Age-related factors may also help explain variability in attack rates, and the size and impact of influenza epidemics across jurisdictions and between populations. In Canada, such effects have been observed in the apparently increased severity of outbreaks on Indigenous peoples' reserves. The implications of these patterns for vaccine allocation necessitate targeted research to understand age-related vulnerabilities early in an influenza pandemic.

Influenza increases invasive meningococcal disease risk in temperate countries.

OBJECTIVES: Invasive meningococcal disease (IMD) is a severe bacterial infection that displays wintertime seasonality in temperate countries. Mechanisms driving seasonality are poorly understood and may include environmental conditions and/or respiratory virus infections. We evaluated the contribution of influenza and environmental conditions to IMD risk, using standardized methodology, across multiple geographical regions. METHODS: We evaluated 3276 IMD cases occurring between January 1999 and December 2011 in 11 jurisdictions in Australia, Canada, France and the United States. Effects of environmental exposures and normalized weekly influenza activity on IMD risk were evaluated using a case-crossover design. Meta-analytic methods were used to evaluate homogeneity of effects and to identify sources of between-region heterogeneity. RESULTS: After adjustment for environmental factors, elevated influenza activity at a 2-week lag was associated with increased IMD risk (adjusted odds ratio (OR) per standard deviation increase 1.29; 95% confidence interval, 1.04-1.59). This increase was homogeneous across the jurisdictions studied. By contrast, although associations between environmental exposures and IMD were identified in individual jurisdictions, none was generalizable. CONCLUSIONS: Using a self-matched design that adjusts for both coseasonality and case characteristics, we found that surges in influenza activity result in an acute increase in population-level IMD risk. This effect is seen across diverse geographic regions in North America, France and Australia. The impact of influenza infection on downstream meningococcal risk should be considered a potential benefit of influenza immunization programmes.

Carbapenemase-producing Enterobacterales in hospital drains in Southern Ontario, Canada.

BACKGROUND: Hospital drains may be an important reservoir for carbapenemase-producing Enterobacterales (CPE). AIM: To determine prevalence of CPE in hospital drains exposed to inpatients with CPE, relatedness of drain and patient CPE, and risk factors for drain contamination. METHODS: Sink and shower drains in patient rooms and communal shower rooms exposed to 310 inpatients with CPE colonization/infection were cultured at 10 hospitals. Using short- and long-read whole-genome sequencing, inpatient and corresponding drain CPE were compared. Risk factors for drain contamination were assessed using multi-level modelling. FINDINGS: Of 1209 exposed patient room and communal shower room drains, 53 (4%) yielded 62 CPE isolates in seven (70%) hospitals. Of 49 CPE isolates in patient room drains, four (8%) were linked to prior room occupants. Linked drain/room occupant pairs included Citrobacter freundii ST18 isolates separated by eight single nucleotide variants (SNVs), related blaKPC-containing IncN3-type plasmids (different species), related blaKPC-3-containing IncN-type plasmids (different species), and related blaOXA-48-containing IncL/M-type plasmids (different species). In one hospital, drain isolates from eight rooms on two units were Enterobacter hormaechei separated by 0-6 SNVs. Shower drains were more likely to be CPE-contaminated than hand hygiene (odds ratio: 3.45; 95% confidence interval: 1.66-7.16) or patient-use (13.0; 4.29-39.1) sink drains. Hand hygiene sink drains were more likely to be CPE-contaminated than patient-use sink drains (3.75; 1.17-12.0). CONCLUSION: Drain contamination was uncommon but widely dispersed. Drain CPE unrelated to patient exposure suggests contamination by undetected colonized patients or retrograde (drain-to-drain) contamination. Drain types had different contamination risks.

Survival after percutaneous endoscopic gastrostomy among older residents of Quebec.

CONTEXT: Percutaneous endoscopic gastrostomy has become a mainstay of nutritional support for individuals with swallowing dysfunction. There is little population-based data to guide the use of this intervention in older individuals. OBJECTIVE: To describe the use of percutaneous endoscopic gastrostomy among older residents of Quebec and to evaluate patient characteristics associated with subsequent survival and hospital discharge. DESIGN: A population-based cohort study. SETTING: Quebec, Canada. PATIENTS: 175 individuals with a billing claim for percutaneous endoscopic gastrostomy performed in 1993. MEASUREMENTS: Billing and hospitalization databases were used to collect patient characteristics, medical diagnoses, discharge destinations, and dates of death. The relationships between demographic and diagnostic variables before gastrostomy, and subsequent survival and discharge home, were evaluated using survival analysis. RESULTS: Median survival after gastrostomy was 210 days. Mortality at 30 days was 18.3%. Decreased survival was associated with a previous diagnosis of malignancy (risk ratio (RR) = 1.71; 95% CI, 1.09-2.68); mortality did not increase with increasing age. Of 163 individuals hospitalized at the time of gastrostomy, 42 (26%) were discharged home. Individuals with a previous diagnosis of stroke (RR = 2.80; 95% CI 1.01-7.77) were more likely to be discharged home than other individuals. CONCLUSIONS: Survival after percutaneous endoscopic gastrostomy is poor; the requirement for such a procedure appears to be a marker for severe underlying disease. The greater likelihood of return home after gastrostomy among individuals with stroke suggests that the use of this intervention as an adjunct to rehabilitation is appropriate in these individuals.

Once-daily dosing of aminoglycoside antibiotics.

Improved understanding of the pharmacodynamics and toxicity of aminoglycoside antibiotics has resulted in the study of once-daily dosing regimens. Although studies have suggested a therapeutic advantage and possibly a decrease in toxicity with once-daily administration, these effects have been modest. The cost savings associated with once-daily aminoglycoside administration, however, makes this approach appealing. Although a syndrome of fever, tachycardia, hypotension, and rigors has been associated with once-daily dosing of gentamicin, this appears to have been the result of impurities in the antibiotic from a single offshore supplier. This syndrome has not been associated with other aminoglycoside antibiotics, and the FDA has now withdrawn its recommendation that once-daily aminoglycoside use be avoided. As with any medical regimen, the decision to use once-daily dosing of aminoglycoside agents must take into account special patient characteristics and the disease state being treated. Although once-daily dosing appears effective in limited studies in children, in individuals with neutropenia, and in individuals with cystic fibrosis, its role in gram-positive coccal endocarditis and in individuals with altered volumes of distribution remains uncertain. Further data are needed to clarify the role of once-daily dosing in these situations.

The estimated economic burden of genital herpes in the United States. An analysis using two costing approaches.

BACKGROUND: Only limited data exist on the costs of genital herpes (GH) in the USA. We estimated the economic burden of GH in the USA using two different costing approaches. METHODS: The first approach was a cross-sectional survey of a sample of primary and secondary care physicians, analyzing health care resource utilization. The second approach was based on the analysis of a large administrative claims data set. Both approaches were used to generate the number of patients with symptomatic GH seeking medical treatment, the average medical expenditures and estimated national costs. Costs were valued from a societal and a third party payer's perspective in 1996 US dollars. RESULTS: In the cross-sectional study, based on an estimated 3.1 million symptomatic episodes per year in the USA, the annual direct medical costs were estimated at a maximum of $984 million. Of these costs, 49.7% were caused by drug expenditures, 47.7% by outpatient medical care and 2.6% by hospital costs. Indirect costs accounted for further $214 million. The analysis of 1,565 GH cases from the claims database yielded a minimum national estimate of $283 million direct medical costs. CONCLUSIONS: GH appears to be an important public health problem from the health economic point of view. The observed difference in direct medical costs may be explained with the influence of compliance to treatment and possible undersampling of subpopulations in the claims data set. The present study demonstrates the validity of using different approaches in estimating the economic burden of a specific disease to the health care system.

Intravenous immunoglobulin, blood viscosity and myocardial infarction.

Polyvalent intravenous immunoglobulin (IVIg) is considered to be standard therapy for a variety of autoimmune and idiopathic disorders. Several reports have emphasized the temporal association between administration of IVIg and thrombotic events. Recent experience with a patient who suffered a large myocardial infarction shortly after receiving IVIg led the authors to review the clinical and basic literature on administration of IVIg as a possible precipitant for myocardial infarction. Although the existence of an association between IVIg administration and myocardial ischemia has not been demonstrated in clinical trials, a body of clinical experience has begun to accumulate that is suggestive of an association between IVIg administration and cardiac and cerebral ischemia in older individuals or individuals with a known history of ischemic disease. Basic research demonstrating that IVIg administration may increase blood viscosity suggests that such an association is plausible.

Echocardiographic detection of pulmonary embolism in transit: implications for institution of thrombolytic therapy.

Right atrial or ventricular thrombi in patients with pulmonary embolism are emboli in transit and are a medical emergency because they are associated with a high mortality rate when treated conservatively with anticoagulation. The current standard therapy is less well accepted because of the risk of clot fragmentation and distal embolization. A case in which an unsuspected right ventricular thrombus was diagnosed by echocardiography is reported. This findings led to treatment with streptokinase (250,000 U, followed by 100,000 U/h for 24 h). Clinical improvement was rapidly obtained and the thrombus disappeared 10 h after the initial study. There was no complication. The case illustrates the utility of two-dimensional enchocardiography in the evaluation of patients with pulmonary embolic disease and the efficacy and safety of thrombolytic therapy in the treatment of pulmonary embolism in transit.

Epidemiological evaluation of spatiotemporal and genotypic clustering of Mycobacterium tuberculosis in Ontario, Canada.

BACKGROUND: In Canada, tuberculosis (TB) rates are at a historic low, with the remaining risk concentrated in a few vulnerable population subgroups. OBJECTIVES: To describe the epidemiology of TB in the Canadian province of Ontario and to characterise risk factors associated with transmission events, identified using genetic typing techniques. DESIGN: Retrospective analysis of 2186 culture-positive TB cases between August 2007 and December 2011. Temporal trends and risk of spatiotemporal and genotypic clustering were evaluated using Poisson and logistic regression models. RESULTS: Being in a spatiotemporal cluster was associated with Aboriginal status (odds ratio [OR] 3.63, 95% confidence interval [CI] 1.23-10.71). Cases in genotypic clusters were more likely to report homelessness as a risk factor (adjusted OR [aOR] 2.92, 95%CI 1.74-4.90) or be male (aOR 1.35, 95%CI 1.09-1.68), and were less likely to be aged ≥ 65 years (aOR 0.63, 95%CI 0.49-0.82), foreign-born (aOR 0.32, 95%CI 0.24-0.43) or Aboriginal (aOR 0.40, 95%CI 0.16-0.99). The Beijing lineage had an annual rate of increase of almost 10% (P = 0.047), and was associated with genotypic clustering (aOR 2.84, 95%CI 2.19-3.67). CONCLUSION: Genotypic data suggest that disease clusters are smaller, but far more common, than would be estimated using spatiotemporal clustering.

Changing epidemiology of invasive Haemophilus influenzae in Ontario, Canada: evidence for herd effects and strain replacement due to Hib vaccination.

The epidemiology of invasive Haemophilus influenzae infections was evaluated in Ontario between 1989 and 2007 to assess the impact of the introduction of the conjugate H. influenzae serotype b (Hib) vaccine in the early 1990 s on Hib and non-Hib serotypes in both vaccinated and unvaccinated cohorts as well as the possibility of "strain replacement" with non-vaccine H. influenzae strains. Data were collected by the provincial Public Health Laboratories-Toronto, Ontario Agency for Health Protection and Promotion, which performed almost all serotyping on invasive (blood, CSF, other sterile sites) H. influenzae strains isolated in the province during the study period. Temporal trends for Hib, other typeable strains, and non-typeable H. influenzae were evaluated by Poisson regression, controlling for the specimen submissions. Prior to infant Hib vaccination, the most commonly observed serotype was serotype b (64.9%). Subsequently, 70.3%, 13.6%, and 9.4% of isolates were non-typeable, serotype f, and serotype b, respectively. Infant Hib vaccination resulted in a decrease in Hib incidence in all age groups (pooled IRR 0.432) and marked increases of non-typeable and serotype f H. influenzae in children aged <5 years (IRR 2.4 and 3.0, respectively). Vaccination against Hib has altered the epidemiology of invasive H. influenzae infections in Ontario. Prevention of invasive Hib disease was observed in both vaccinated and unvaccinated age groups. Invasive H. influenzae infection now commonly presents as sepsis due to non-typeable H. influenzae in older individuals. However, strain replacement of Hib with serotype f and non-typeable strains in children under 5 years was documented.

Health related quality of life in genital herpes: a pilot comparison of measures.

BACKGROUND: Genital herpes (GH) is a common sexually transmitted infection. Novel tools for the control of GH (for example, tests and vaccines) are emerging, but optimal assessment of the cost effectiveness of such interventions requires scaled, preference based estimates of the impact of GH on health related quality of life. METHODS: We provided self administered interviews to 39 individuals with recurrent GH recruited from an STD clinic and a GH support group in southern Ontario, Canada. Health preference estimates were generated using visual analogue scales (VAS), a time-tradeoff approach (TTO) and the Health Utilities Index Mark-II (HUI-II). Quality of life was also assessed with the Recurrent Genital Herpes Quality of Life scale (RGHQoL). RESULTS: Average (SD) health values for asymptomatic and symptomatic genital herpes were 0.89 (0.21) and 0.89 (0.22) using TTO, and 0.76 (0.30) and 0.71 (0.30) using VAS. Health utility estimates generated with HUI-II for transient symptomatic and asymptomatic health states were 0.93 (0.08) and 0.80 (0.16). Log transformed health value estimates exhibited convergent validity when compared to RGHQoL, as did health utility estimates for symptomatic GH. Utility scores for symptomatic GH increased (improved) with increasing age; no other subject characteristic was predictive of preference weights. CONCLUSIONS: Preference based measures of health related quality of life can be elicited with relative ease in the context of genital herpes, and preference weights are correlated with quality of life scores generated using the RGHQoL. Generation of preference weights will permit direct comparison of the economic attractiveness of herpes prevention interventions with that of other commonly available health interventions.

Hemophagocytic syndromes and infection.

Hemophagocytic lymphohistiocytosis (HLH) is an unusual syndrome characterized by fever, splenomegaly, jaundice, and the pathologic finding of hemophagocytosis (phagocytosis by macrophages of erythrocytes, leukocytes, platelets, and their precursors) in bone marrow and other tissues. HLH may be diagnosed in association with malignant, genetic, or autoimmune diseases but is also prominently linked with Epstein-Barr (EBV) virus infection. Hyperproduction of cytokines, including interferon-gamma and tumor necrosis factor-alpha, by EBV- infected T lymphocytes may play a role in the pathogenesis of HLH. EBV-associated HLH may mimic T-cell lymphoma and is treated with cytotoxic chemotherapy, while hemophagocytic syndromes associated with nonviral pathogens often respond to treatment of the underlying infection.

Intrapleural placement of a nasogastric tube: an unusual complication of nasotracheal intubation.

PURPOSE: Although rare, the misplacement of nasogastric tubes into the pleural space has been described. The prognosis of such injuries is improved by prompt recognition; therefore, it is important for physicians who practice nasogastric intubation to be aware of this potential complication, and to be familiar with an approach to early diagnosis. CLINICAL FEATURES: We present a case of perforation of the cervical oesophagus by a polyvinylchloride nasogastric tube, following a traumatic attempt at nasotracheal intubation. This resulted in passage of the nasogastric tube into the pleural space. CONCLUSIONS: Our experience with this case and a review of the relevant literature suggest that such trauma may predispose to malplacement of nasogastric tubes. Clinical signs, such as aspiration of fluid from a nasogastric tube, and auscultation of air insufflated into the stomach, are unreliable; however, the presence of subcutaneous air in the neck on chest radiograph, and the presence of cervical crepitance on physical examination, are valuable signs in the early diagnosis of perforation of the cervical oesophagus. Contrast oesophagography remains the diagnostic manoeuvre of choice in confirming the diagnosis, but early diagnosis will depend on a high index of suspicion and prompt viewing of chest x-rays. The management and the prognosis of such injuries depends on the level of the perforation, delays in diagnosis, and the presence of associated mediastinitis.

Estimating the costs and benefits of screening monogamous, heterosexual couples for unrecognised infection with herpes simplex virus type 2.

OBJECTIVES: Herpes simplex virus type 2 (HSV-2) is the most common cause of ulcerative genital disease in the United States, but infection is commonly unrecognised. Serological screening tests could identify discordantly infected couples and permit targeted interventions to limit HSV-2 transmission. Our objective was to evaluate the projected cost effectiveness of strategies to prevent HSV-2 transmission in couples with no history of HSV-2 infection. METHODS: We created a mathematical model to simulate the natural history and costs of HSV-2 transmission, and the expected impact of HSV-2 prevention strategies in monogamous, heterosexual couples. Strategies evaluated included (i) no screening; (ii) universal condom use; and (iii) serological screening for HSV-2 with condom use targeted to discordant couples. Screening tests considered included western blot (WB), ELISA, and ELISA with confirmation of positive test results using WB (ELISA-->WB). RESULTS: Compared to no screening, the use of ELISA-->WB prevented 38 future infections per 1000 couples, with a cost effectiveness ratio of $8200 per infection averted. The use of WB in all couples had an incremental cost effectiveness ratio of $63 600 per infection averted. Strategies of ELISA alone and universal condom use were not cost effective. The cost effectiveness of ELISA-->WB improved with increasing prevalence of HSV-2, but worsened with decreasing condom compliance. Screening with ELISA alone was a reasonable strategy only when ELISA specificity increased to 99%. CONCLUSIONS: Serological screening for unrecognised HSV-2 infection in monogamous, heterosexual couples is expected to decrease the incidence of HSV-2 infection, but increase healthcare costs. For couples choosing to be screened, a two step testing strategy (ELISA-->WB) is recommended. Recommendations for a national policy to conduct serological screening will depend on the value placed on averting an incident HSV-2 infection.

Clinical effectiveness and cost-effectiveness of 2 management strategies for infected total hip arthroplasty in the elderly.

Optimal management of infected total hip arthroplasty poses a major challenge to clinicians. Exchange arthroplasty is usually advocated but has high rates of surgical morbidity and is expensive. Debridement with prosthesis retention is associated with less morbidity, but high rates of relapsed infection have been described. To estimate the effectiveness and cost-effectiveness of these 2 strategies among older patients, we used a Markov model to simulate patients' projected lifetime clinical course in hypothetical cohorts of 65-year-old and frail 80-year-old men and women. Initial debridement and retention increased life expectancy 2.2-2.6 quality-adjusted life months and had a favorable cost-effectiveness ratio in all cohorts. Results were most sensitive to the annual rate of relapse after debridement and age at initial diagnosis of infection. In the absence of prospective clinical trials, debridement and retention is a reasonable strategy for treatment of older persons with staphylococcal or streptococcal infection and a nonloosened prosthesis.