A Systematic Literature Review on Risk Factors for and Timing of Clostridioides difficile Infection in the United States.

INTRODUCTION: Clostridioides difficile infection (CDI) is a major public health threat. Up to 40% of patients with CDI experience recurrent CDI (rCDI), which is associated with increased morbidity. This study aimed to define an at-risk population by obtaining a detailed understanding of the different factors leading to CDI, rCDI, and CDI-related morbidity and of time to CDI. METHODS: We conducted a systematic literature review (SLR) of MEDLINE (using PubMed) and EMBASE for relevant articles published between January 1, 2016, and November 11, 2022, covering the US population. RESULTS: Of the 1324 articles identified, 151 met prespecified inclusion criteria. Advanced patient age was a likely risk factor for primary CDI within a general population, with significant risk estimates identified in nine of 10 studies. Older age was less important in specific populations with comorbidities usually diagnosed at earlier age, such as bowel disease and cancer. In terms of comorbidities, the established factors of infection, kidney disease, liver disease, cardiovascular disease, and bowel disease along with several new factors (including anemia, fluid and electrolyte disorders, and coagulation disorders) were likely risk factors for primary CDI. Data on diabetes, cancer, and obesity were mixed. Other primary CDI risk factors were antibiotics, proton pump inhibitors, female sex, prior hospitalization, and the length of stay in hospital. Similar factors were identified for rCDI, but evidence was limited. Older age was a likely risk factor for mortality. Timing of primary CDI varied depending on the population: 2-3 weeks in patients receiving stem cell transplants, within 3 weeks for patients undergoing surgery, and generally more than 3 weeks following solid organ transplant. CONCLUSION: This SLR uses recent evidence to define the most important factors associated with CDI, confirming those that are well established and highlighting new ones that could help to identify patient populations at high risk.

Multiple Sources of the Outbreak of Legionnaires' Disease in Genesee County, Michigan, in 2014 and 2015.

BACKGROUND: A community-wide outbreak of Legionnaires' disease (LD) occurred in Genesee County, Michigan, in 2014 and 2015. Previous reports about the outbreak are conflicting and have associated the outbreak with a change of water source in the city of Flint and, alternatively, to a Flint hospital. OBJECTIVE: The objective of this investigation was to independently identify relevant sources of Legionella pneumophila that likely resulted in the outbreak. METHODS: An independent, retrospective investigation of the outbreak was conducted, making use of public health, health care, and environmental data and whole-genome multilocus sequence typing (wgMLST) of clinical and environmental isolates. RESULTS: Strong evidence was found for a hospital-associated outbreak in both 2014 and 2015: a) 49% of cases had prior exposure to Flint hospital A, significantly higher than expected from Medicare admissions; b) hospital plumbing contained high levels of L. pneumophila; c) Legionella control measures in hospital plumbing aligned with subsidence of hospital A-associated cases; and d) wgMLST showed Legionella isolates from cases exposed to hospital A and from hospital plumbing to be highly similar. Multivariate analysis showed an increased risk of LD in 2014 for people residing in a home that received Flint water or was located in proximity to several Flint cooling towers. DISCUSSION: This is the first LD outbreak in the United States with evidence for three sources (in 2014): a) exposure to hospital A, b) receiving Flint water at home, and c) residential proximity to cooling towers; however, for 2015, evidence points to hospital A only. Each source could be associated with only a proportion of cases. A focus on a single source may have delayed recognition and remediation of other significant sources of L. pneumophila. https://doi.org/10.1289/EHP5663.

Outbreaks of meningococcal B infection and the 4CMenB vaccine: historical and future perspectives.

Strains of Neisseria meningitidis serogroup B (MenB) causing invasive meningococcal disease are genetically diverse; however, only a small number of hyperinvasive lineages (CC32, CC41/44, CC269 and CC162) have dominated during the global spread over the past 50 years. Since the mid-1970s, major outbreaks and hyperendemic disease have been reported in Norway, Cuba, France, Canada, New Zealand (and elsewhere), most recently in the USA. We characterized the epidemiology of these MenB outbreaks and their associated clonal complexes and retrospectively assessed the potential coverage offered by the 4CMenB vaccine, a four-component vaccine developed to help confer protection against a broad range of meningococcal B strains causing disease. Of 21 isolates from four clonal complexes evaluated using both human Serum Bactericidal Assay and the Meningococcal Antigen Testing System, coverage ranged from 67 to 100%. 4CMenB shows good potential as a candidate vaccine to be used in the control of new MenB outbreaks globally.

Utility of the first few100 approach during the 2009 influenza A(H1N1) pandemic in the Netherlands.

BACKGROUND: To guide policy and control measures, decent scientific data are needed for a comprehensive assessment of epidemiological, clinical and virological characteristics of the First Few hundred (FF100) cases. We discuss the feasibility of the FF100 approach during the 2009 pandemic and the added value compared with alternative data sources available. METHODS: The pandemic preparedness plan enabled us to perform a case-control study, assessing patient characteristics and risk factors for experiencing symptomatic influenza A(H1N1)2009 infection and providing insight into transmission. We assessed to what extent timely and novel data were generated compared to other available data sources. RESULTS: In May-December 2009, a total of 68 cases and 48 controls were included in the study. Underlying non-respiratory diseases were significantly more common among cases compared to controls, while a protective effect was found for frequent hand washing. Seroconversion was found for 7/30 controls (23%), and persisting high titers for 4/30 controls (13%). The labour-intensive study design resulted in slow and restricted recruitment. CONCLUSIONS: The findings of our case-control study gave new insights in transmission risks and possible interventions for improved control. Nevertheless, the FF100 approach lacked timeliness and power due to limited recruitment. For future pandemics we suggest pooling data from several countries, to enable collecting sufficient data in a relatively short period.

Q fever among culling workers, the Netherlands, 2009-2010.

In 2009, dairy goat farms in the Netherlands were implicated in >2,300 cases of Q fever; in response, 51,820 small ruminants were culled. Among 517 culling workers, despite use of personal protective equipment, 17.5% seroconverted for antibodies to Coxiella burnetii. Vaccination of culling workers could be considered.

Determinants of malaria prophylaxis among German travelers to Kenya, Senegal, and Thailand.

BACKGROUND: Malaria chemoprophylaxis is a mainstay of malaria prevention in travelers. Adequate pretravel advice forms the basis for efficient malaria prophylaxis. This study assessed the determinants for seeking pretravel advice and evaluated the quality of advice from each source and its influence on the patterns and outcome of malaria prophylaxis intake. METHODS: In March and April 2004, a self-administered questionnaire was distributed by cabin crews to passengers flying back to Germany from three popular tourist destinations: Kenya, Senegal, and Thailand. To evaluate the quality of advice and actual intake, figures were assessed against the official recommendations of the German Society of Travel Medicine and International Health (DTG). RESULTS: A total of 1,001 passengers were included in the study (Kenya, 492; Senegal, 131; and Thailand, 378), of which 81% had sought any kind of pretravel health advice. Travelers' age and time of pretravel consultation were associated with the source of information consulted. Seventy-five percent of travelers from Senegal and Kenya received DTG compliant advice compared to only 17% of travelers from areas with low malaria risk in Thailand. Travelers returning from Kenya and Senegal had used correct chemoprophylaxis in only 65 and 47% of trips, respectively. In multivariate analysis, the factors determining correct intake among Senegal and Kenya travelers were receiving pretravel advice (from nonmedical professionals: OR 4.4, 95% CI 1.9-10.0 and from medical professionals: OR 15.4, 95% CI 7.3-32.4), a correct risk perception (OR 2.9, 95% CI 1.9-4.5), 2 to 3 weeks of travel abroad (vs a duration >3 wk: OR 2.2, 95% CI 1.3-3.8), and travel to Kenya (OR 1.9, 95% CI 1.1-3.1). CONCLUSIONS: Malaria prevention among a large proportion of German travelers to tropical destinations is inadequate. Public health efforts should be made to raise awareness among travelers, travel agencies, and medical institutions in Germany.

Detecting emerging transmissibility of avian influenza virus in human households.

Accumulating infections of highly pathogenic H5N1 avian influenza in humans underlines the need to track the ability of these viruses to spread among humans. A human-transmissible avian influenza virus is expected to cause clusters of infections in humans living in close contact. Therefore, epidemiological analysis of infection clusters in human households is of key importance. Infection clusters may arise from transmission events from (i) the animal reservoir, (ii) humans who were infected by animals (primary human-to-human transmission), or (iii) humans who were infected by humans (secondary human-to-human transmission). Here we propose a method of analysing household infection data to detect changes in the transmissibility of avian influenza viruses in humans at an early stage. The method is applied to an outbreak of H7N7 avian influenza virus in The Netherlands that was the cause of more than 30 human-to-human transmission events. The analyses indicate that secondary human-to-human transmission is plausible for the Dutch household infection data. Based on the estimates of the within-household transmission parameters, we evaluate the effectiveness of antiviral prophylaxis, and conclude that it is unlikely that all household infections can be prevented with current antiviral drugs. We discuss the applicability of our method for the detection of emerging human-to-human transmission of avian influenza viruses in particular, and for the analysis of within-household infection data in general.

Measurement of antibodies to avian influenza virus A(H7N7) in humans by hemagglutination inhibition test.

During the epizootic of highly pathogenic avian influenza A(H7N7) in 2003 in The Netherlands, RT-PCR and culture confirmed infection was detected in 89 persons who were ill. A modified hemagglutination inhibition (HI) test using horse erythrocytes and 2 hemagglutinating units of virus was applied to assess retrospectively the extent of human (subclinical) infection. Validation of the HI-test with sera from 34 RT-PCR and culture confirmed A(H7) infected persons and sera from 100 persons from a human influenza vaccine trial in autumn 2002 showed that this HI-test had a sensitivity of 85% and a specificity of 100% when using a cut-off titer of > or =10. Using this cut-off value, A(H7) specific antibodies were detected in 49% of 508 persons exposed to poultry and in 64% of 63 persons exposed to A(H7) infected persons. Correlation of seropositivity with the occurrence of eye symptoms in exposed persons who had not received antiviral prophylaxis and of reduced seropositivity with taking antiviral prophylaxis provided further evidence that the A(H7) HI antibody titers were real. In conclusion, by applying an HI-test using horse erythrocytes human antibodies against the avian A(H7N7) virus were detected with high sensitivity and specificity in an unexpectedly high proportion of exposed persons.

Nationwide survey of the role of travel medicine in primary care in Germany.

BACKGROUND: With more persons traveling to (sub)tropical destinations, travel medicine is an increasing challenge for the health care system in many countries. This study investigated the role and scope of travel medicine provided by general practitioners (GPs) in primary health care, assessed the determinants of specific prophylactic recommendations, and identified the needs of GPs regarding training and cooperation in travel medicine. METHODS: A national survey was conducted among randomly selected GPs in Germany. Information on the type and extent of activities in travel medicine, the number and characteristics of patients, the use of specific information systems, and training and cooperation, was obtained with a standardized postal questionnaire. Representativeness was assessed by a computer-assisted telephone survey among nonrespondents. Univariate and multivariate statistical analysis was performed. RESULTS: Of all GPs (n=1,320), 95% provided medical pretravel advice or post-travel counseling (13.2 patients/month). The most common topics in pretravel consultation were immunizations (95%), malaria chemoprophylaxis (94%), advice on exposure prophylaxis (41%), and advice on protection from sexually transmitted infections (STIs) (43%). GPs frequently advised certain patient groups (e.g., cardiovascular patients 68%, pregnant women 20%). Travelers' diarrhea was the most common topic in post-travel consultation (89%), followed by fever (38%). Of the GPs, 25% cooperated regularly with institutions with special expertise in travel medicine or tropical diseases. Sixty-four percent had received some training in travel medicine, and 86% stated a need for additional training. In the multivariate analysis, independent determinants for advice on exposure prophylaxis and STI risks included special training in travel medicine, use of country-specific information sources, and location of the practice in the former West Germany and urban areas. CONCLUSIONS: Travel medicine is of importance in primary health care in Germany. There is a need for improved counseling on exposure and STI prophylaxis. GPs' training in travel medicine and cooperation with institutions such as institutes, clinics and laboratories for tropical medicine should be improved.