Invasive Haemophilus influenzae Disease,Europe, 1996–2006

An international collaboration was established in 1996 to monitor the impact of routine Haemophilus influenzae type b (Hib) vaccination on invasive H. influenzae disease; 14 countries routinely serotype all clinical isolates. Of the 10,081 invasive H. influenzae infections reported during 1996–2006, 4,466 (44%, incidence 0.28 infections/100,000 population) were due to noncapsulated H. influenzae (ncHi); 2,836 (28%, 0.15/100,000), to Hib; and 690 (7%, 0.036/100,000), to non–b encapsulated H. influenzae. Invasive ncHi infections occurred in older persons more often than Hib (median age 58 years vs. 5 years, p<0.0001) and were associated with higher case-fatality ratios (12% vs. 4%, p<0.0001), particularly in infants (17% vs. 3%, p<0.0001). Among non-b encapsulated H. influenzae, types f (72%) and e (21%) were responsible for almost all cases; the overall case-fatality rate was 9%. Thus, the incidence of invasive non–type b H. influenzae is now higher than that of Hib and is associated with higher case fatality.     

Haemophilus influenzae Serotype a Invasive Disease,Alaska, USA, 1983–2011

Before introduction of Haemophilus influenzae type b (Hib) vaccines, rates of Hib disease in Alaska’s indigenous people were among the highest in the world. Vaccination reduced rates dramatically; however, invasive H. influenzae type a (Hia) disease has emerged. Cases of invasive disease were identified through Alaska statewide surveillance during1983–2011. Of 866 isolates analyzed for serotype, 32 (4%) were Hia. No Hia disease was identified before 2002; 32 cases occurred during 2002–2011 (p<0.001). Median age of case-patients was 0.7 years; 3 infants died. Incidence of Hia infection (2002–2011) among children <5 years was 5.4/100,000; 27 cases occurred in Alaska Native children (18/100,000) versus 2 cases in non-Native children (0.5/100,000) (risk ratio = 36, p<0.001). From 12/2009 to 12/2011, 15 cases of Hia disease occurred in southwestern Alaska (in children <5 years, rate = 204/100,000). Since introduction of the Hib conjugate vaccine, Hia infection has become a major invasive bacterial disease in Alaska Native children.     

Epidemiology of Serotype 1 Invasive Pneumococcal Disease,South Africa, 2003–2013

In South Africa, 7-valent pneumococcal conjugate vaccine (PCV) was introduced in April 2009 and replaced with 13-valent PCV in April 2011. We describe the epidemiology of serotype 1 Streptococcus pneumoniae disease during the pre- and post-PCV eras (2003–2013). Using laboratory-based invasive pneumococcal disease (IPD) surveillance, we calculated annual incidences, identified IPD clusters, and determined serotype 1–associated factors. Of 46,483 IPD cases, 4,544 (10%) were caused by serotype 1. Two clusters of serotype 1 infection were detected during 2003–2004 and 2008–2012, but incidence decreased after 2011. Among children <5 years of age, those who had non–serotype 1 IPD had shorter hospital stays, fewer cases of penicillin-nonsusceptible disease, and lower HIV prevalence and in-hospital death rates than did those with serotype 1 IPD; similar factors were noted for older patients. Serotype 1 IPD had distinctive clinical features in South Africa, and annual incidences fluctuated, with decreases noted after the introduction of PCV13.     

Impact of New-Generation Lipid Emulsions on Cellular Mechanisms of Parenteral Nutrition–Associated Liver Disease

Parenteral nutrition (PN) is a life-saving nutritional support for a large population of hospitalized infants, and lipids make a substantial contribution to their energy and essential fatty acid (FA) needs. A challenge in the care of these infants is that their metabolic needs require prolonged PN support that increases the risk of PN-associated liver disease (PNALD). In recent years, the emergence of new parenteral lipid emulsions containing different source lipids and FA profiles has created nutritional alternatives to the first-generation, soybean oil–based lipid emulsion Intralipid. The limited U.S. introduction of the new-generation fish-oil emulsion Omegaven has generated promising results in infants with PNALD and spawned a renewed interest in how PN and lipid emulsions, in particular, contribute to this disease. Studies suggest that the lipid load and constituents, such as specific FAs, ratio of n–3 (ω-3) to n–6 (ω-6) long-chain polyunsaturated FAs, phytosterols, and vitamin E content, may be involved. There is an existing literature describing the molecular mechanisms whereby these specific nutrients affect hepatic metabolism and function via lipid and bile acid sensing nuclear receptors, such as peroxisome proliferator–activated receptor α, liver X receptor, and farnesoid X receptor, yet virtually no information as to how they interact and modulate liver function in the context of PN in pediatric patients or animal models. This article will review the recent development of parenteral lipid emulsions and their influence on PNALD and highlight some of the emerging molecular mechanisms that may explain the effects on liver function and disease.     

Is Dietitian Use Associated with Celiac Disease Outcomes?

A gluten-free diet (GFD) is the treatment for celiac disease (CD), but due to its complexity, dietitian referral is uniformly recommended. We surveyed patients with CD to determine if dietitian use is associated with quality of life, symptom severity, or GFD adherence. The survey utilized three validated CD-specific instruments: the CD quality of life (CD-QOL), CD symptom index (CSI) and CD adherence test (CDAT). Four hundred and thirteen patients with biopsy-proven CD were eligible for inclusion. The majority (77%) were female and mean BMI was 24.1. Over three-quarters of patients (326, 79%) had seen a dietitian, however, 161 (39%) had seen a dietitian only once. Age, sex, and education level were not associated with dietitian use; nor was BMI (24.6 vs. 24.0, p = 0.45). On multivariate analysis, adjusting for age gender, education, duration of disease, and body mass index, dietitian use was not associated with CD-QOL, CSI, or CDAT scores. Our survey did not show an association between dietitian use and symptom severity, adherence, or quality of life. Delay in diagnosis was associated with poorer outcomes. This is a preliminary study with several limitations, and further prospective analysis is needed to evaluate the benefits and cost-effectiveness of dietitian-referral in the care of celiac disease patients.     

Effects of Disease Misclassification on Exposure–Disease Association

Objectives. We explore how misclassification in disease status can distort the exposure–disease association in a study with dichotomous disease and exposure status.Methods. We define the difference in population odds ratios between populations with and without disease misclassification as population-level bias and derive the bias as a function of sensitivity and specificity for observed disease status. The magnitude and direction of bias can be elucidated through analytic derivations, as illustrated with numerical examples.Results. Patterns of bias exist not only for nondifferential misclassification but also for some differential misclassification scenarios. We have provided conditions defined in terms of sensitivity and specificity that correspond to each pattern of bias.Conclusions. Caution is needed in interpreting results when misclassification is present. Our findings can be used to assess the effects of disease misclassification in a population when sensitivity and specificity are known or can be estimated.In epidemiological and clinical studies, we are often interested in the association between a dichotomous exposure and a dichotomous health outcome such as disease status. However, misclassification is often present in these measures when the gold standard assessment is too expensive to apply and a more affordable but less accurate assessment is used instead. For example, misclassification for disease status is likely to occur when psychiatric disorder status is assessed through self-reported surveys instead of in-person clinical diagnosis. Likewise, misclassification for exposure status is likely to occur when individual exposure to air pollution is assessed by measurements recorded at neighborhood monitoring stations rather than by personal monitoring devices.Misclassification can alter the odds ratio (OR) that measures the exposure–disease association in a population. This difference can sometimes present significant problems in drawing conclusions about the nature and strength of the exposure–disease association, because the direction of the deviation is unclear and the magnitude of the deviation can be large. Here we focus on the impact of disease misclassification on the exposure–disease relationship when the exposure category is correctly classified.Two types of disease misclassification can arise in an exposure–disease association study: nondifferential and differential. Nondifferential misclassification occurs when neither sensitivity nor specificity for disease classification varies by exposure category. By contrast, differential misclassification occurs when misclassification of disease status varies by exposure category.1,2 It is usually believed that nondifferential misclassification in either exposure or disease status results in an estimate that has the same sign as the true association but reduced magnitude, unless the misclassification is so severe that the estimate might switch over to the opposite side of the null.3–9 However, differential misclassification can have effects with indeterminate direction,6 away from the null, toward the null, or even switched to the opposite side of the null. It is unclear what conditions cause specific deviations. Chyou studied patterns of effects in the OR estimation attributable to differential misclassification by case–control status in a case–control study, with limited numerical examples.10 However, conclusions based on limited numerical examples may be sensitive to the conditions chosen for the study. Thus it is desirable to use analytic derivation to examine the pattern of misclassification effects in the exposure–disease association, especially when differential misclassification occurs.Here we focus on the difference in population parameters (here the OR) between populations with and without disease misclassification, referred to as population-level bias. This population-level bias is different from the bias of an estimator, which represents the difference between an estimator’s expectation and the true value of the parameter being estimated. For sample-based estimation, the parameters estimated are consistent asymptotically for the corresponding population parameters; thus the patterns of bias for the sample estimators are the same asymptotically as the patterns for the population parameters. We focus on population parameters without estimation error and refer to population-level bias simply as bias.     

Legionnaires' Disease and Associated Comorbid Conditions as Causes of Death in the U.S., 2000–2010

ObjectiveRecent U.S. outbreaks of Legionnaires'' disease (LD) underscore the virulent nature of this infectious pneumonia. To date, only a paucity of literature has described the mortality burden of LD. This study updates LD mortality using U.S. multiple-cause-of-death data from 2000–2010.MethodsWe calculated crude and age-adjusted rates for LD mortality for age, sex, race, state, Census region, and year. We conducted Poisson regression to assess seasonal and temporal trends. We generated matched odds ratios (MORs) to describe the association between LD-related deaths and other comorbid conditions listed on the death certificates.ResultsWe identified a total of 1,171 LD-related deaths during 2000–2010. The age-adjusted mortality rate remained relatively static from 2000 (0.038 per 100,000 population, 95% confidence interval [CI] 0.031, 0.046) to 2010 (0.040 per 100,000 population, 95% CI 0.033, 0.047). The absolute number increased from 107 to 135 deaths during this period, with adults ≥45 years of age having the highest caseload. Overall, LD mortality rates were 2.2 times higher in men than in women. White people accounted for nearly 83.3% of all LD-related deaths, but the age-adjusted mortality rates for black and white people were similar. Comorbid conditions such as leukemia (MOR=4.8, 95% CI 3.5, 6.6) and rheumatoid arthritis (MOR=5.6, 95% CI 3.3, 9.4) were associated with LD diagnosis on death certificates.ConclusionComorbid conditions that could lead to an immunocompromised state were associated with fatal LD on U.S. death certificates. Characterization of LD mortality burden and related comorbidities has practice implications for clinical medicine and public health surveillance.Legionnaires'' disease (LD) is a severe form of pneumonia that can become fatal in vulnerable individuals.^1–5 The condition is caused by the gram-negative bacterium Legionella pneumophila, a naturally occurring organism found in water.^2,3 The organism is primarily transmitted to humans through inhalation of contaminated aerosolized water droplets. Typical sources of outbreaks include, but are not limited to, hot tubs, hot water tanks, large plumbing systems, decorative fountains, and cooling towers. The pneumophila species is generally not found in car or window air-conditioners.^1–4 To date, no person-to-person transmission has been documented.^1–4,6,7Risk factors that increase susceptibility to LD include advanced age, smoking, chronic lung disease, and having a weak or suppressed immune system.^1–4,6,7 Among individuals with a weakened immunity, those with cancer, diabetes, or kidney failure are particularly at risk. Although human immunodeficiency virus (HIV) infection has been linked to more severe infections, LD is generally not more common among people with HIV/acquired immunodeficiency syndrome (AIDS).^1,8,9 More than 20% of cases in the United States reported to the Centers for Disease Control and Prevention (CDC) each year are travel-related.³ Nosocomial transmissions of LD can be problematic, as at-risk individuals are plentiful and plumbing in hospital facilities is often old.^1,4 Because in-house diagnostic testing is readily available, detection of LD is more likely in the hospital setting.⁴ Currently, CDC recommends urinary antigen assay and a culture of respiratory secretions on selective media as the diagnostic tests of choice for confirming Legionella infection.³Annually, CDC estimates that as many as 18,000 individuals are hospitalized with LD in the U.S.³ However, this number is considered an underestimate, as the disease is often underreported due in part to its diagnostic complexity and its resemblance to other pneumonias with similar symptom presentations.^3,7 Symptoms of LD include cough, shortness of breath, fever, muscle aches, and headaches; they often start shortly after exposure to the bacteria.^1–4,6Recent LD outbreaks in the Veterans Affairs (VA) Medical Center in Pittsburgh, Pennsylvania, and in a retirement community in Ohio affirm the virulent nature of this infection and underscore the importance of the causative infectious pathogen to clinical practice and public health surveillance.^10,11 Based on hospitalizations and treatment data, the annual costs for LD have been estimated at nearly $684 million.¹² Few studies have recently examined LD mortality and its associated comorbid conditions. This study contributes to the closing of this gap in the literature by analyzing the national multiple-cause-of-death (MCD) data to describe the current mortality profile of LD in the U.S., for the period 2000–2010.     

Invasive Meningococcal Disease due to group C N. meningitidis ST11 (cc11): The Tuscany cluster 2015–2016

ObjectivesTo describe the cluster of MenC ST11 Invasive Meningococcal Disease (IMD) occurred in Tuscany in the years 2015–2016.MethodsA retrospective charts analysis of clinical, epidemiological and microbiological aspects of documented IMD was performed. Prognostic factors for death were evaluated.ResultsSixty-one patients with IMD in the 2015–2016 period were documented: 28 had meningococcemia, 24 meningitis plus meningococcemia and 9 meningitis. MenC ST11 (cc11) was identified in 48/54 (89%) of the tested strains. All patients, with the exception of three very early death, received timely and appropriate antibiotic therapy and, in selected case, adjunctive therapy with steroids and Pentaglobin®. Forty-one patients recovered (67.3%, mean age: 26 years), 7 had permanent sequelae (11.3%, mean age 31 years) and 13 died (21.3%; mean age: 46 years). In a multivariate analysis, septic shock, purpura fulminans and advanced age were negative prognostic factors, while emergency admittance to a tertiary-care, university hospital, positively influenced the survival rate. The epidemiological analysis of the cluster identified close contacts and recreational environments such as discos as hotspot for MenC transmission. After a massive vaccination campaign, the number of MenC cases reported in Tuscany in 2017 decreased to 10, with no death.ConclusionsVaccination campaign of key populations together with the need for rapid and qualified emergency care of the affected patients seems to be the main lesson learned by the MenC ST11 Tuscany epidemic.