Procalcitonin to Reduce Long-Term Infection-associated Adverse Events in Sepsis. A Randomized Trial.

Rationale: Although early antimicrobial discontinuation guided by procalcitonin (PCT) has shown decreased antibiotic consumption in lower respiratory tract infections, the outcomes in long-term sepsis sequelae remain unclear.Objectives: To investigate if PCT guidance may reduce the incidence of long-term infection-associated adverse events in sepsis.Methods: In this multicenter trial, 266 patients with sepsis (by Sepsis-3 definitions) with lower respiratory tract infections, acute pyelonephritis, or primary bloodstream infection were randomized (1:1) to receive either PCT-guided discontinuation of antimicrobials or standard of care. The discontinuation criterion was ≥80% reduction in PCT levels or any PCT ≤0.5 µg/L at Day 5 or later. The primary outcome was the rate of infection-associated adverse events at Day 180, a composite of the incidence of any new infection by Clostridioides difficile or multidrug-resistant organisms, or any death attributed to baseline C. difficile or multidrug-resistant organism infection. Secondary outcomes included 28-day mortality, length of antibiotic therapy, and cost of hospitalization.Measurements and Main Results: The rate of infection-associated adverse events was 7.2% (95% confidence interval [CI], 3.8-13.1%; 9/125) versus 15.3% (95% CI, 10.1-22.4%; 20/131) (hazard ratio, 0.45; 95% CI, 0.20-0.98; P = 0.045); 28-day mortality 15.2% (95% CI, 10-22.5%; 19/125) versus 28.2% (95% CI, 21.2-36.5%; 37/131) (hazard ratio, 0.51; 95% CI, 0.29-0.89; P = 0.02); and median length of antibiotic therapy 5 (range, 5-7) versus 10 (range, 7-15) days (P < 0.001) in the PCT and standard-of-care arms, respectively. The cost of hospitalization was also reduced in the PCT arm.Conclusions: In sepsis, PCT guidance was effective in reducing infection-associated adverse events, 28-day mortality, and cost of hospitalization.Clinical trial registered with www.clinicaltrials.gov (NCT03333304).

Haplotypes composed of minor frequency single nucleotide polymorphisms of the TNF gene protect from progression into sepsis: A study using the new sepsis classification.

OBJECTIVES: Several articles have provided conflicting results regarding the role of single nucleotide polymorphisms (SNPs) in the promoter region of the TNF gene in susceptibility to sepsis. Former articles have been based on previous definitions of sepsis. This study investigated the influence of TNF haplotypes on the development of sepsis using the new Sepsis-3 definitions. METHODS: DNA was isolated from patients suffering from infection and systemic inflammatory response syndrome. Haplotyping was performed for six SNPs of TNF. The serum levels of tumour necrosis factor alpha (TNF-α) of these patients were measured using an enzyme immunosorbent assay. Patients were classified into infection and sepsis categories using the Sepsis-3 definitions. Associations between the TNF haplotypes and the clinical characteristics and serum TNF-α levels of the patients were examined. RESULTS: The most common TNF haplotype h1 was composed of major alleles of the studied SNPs. Carriage of haplotypes composed of minor frequency alleles was associated with a lower risk of developing sepsis (odds ratio 0.41, 95% confidence interval 0.19-0.88, p=0.022), but this did not affect the 28-day outcome. Serum TNF-α levels were significantly higher among patients homozygous for h1 haplotypes who developed sepsis compared to infection (p=0.032); a similar result was not observed for patients carrying other haplotypes. CONCLUSIONS: Haplotypes containing minor frequency SNP alleles of TNF protect against the development of sepsis without affecting the outcome.

Active surveillance of Q fever in human and animal population of Cyprus.

BACKGROUND: A long-term active surveillance of Q fever was conducted in Cyprus organized in two phases. METHODS: Following serological tests and identification of seropositive humans and animals for C. burnetii in two villages (VIL1 and VIL2), all seronegative individuals were followed up for one year on a monthly basis by trained physicians to detect possible seroconversion for Q fever. In the second phase of the study, active surveillance for one year was conducted in the entire Cyprus. Physicians were following specific case definition criteria for Q fever. Standardized questionnaires, a geographical information system on a regional level, Immunofluorescence Assay (IFA) examinations and shell vial technique were used. RESULTS: Eighty-one seronegative humans and 239 seronegative animals from both villages participated in the first phase surveillance period of Q fever. Despite the small number of confirmed clinical cases (2 humans and 1 goat), a significant percentage of new seropositives for C. burnetii (44.4% of human participants and 13.8% of animals) was detected at the end of the year. During the second phase of surveillance, 82 humans, 100 goats, and 76 sheep were considered suspected cases of Q fever. However, only 9 human, 8 goat, and 4 sheep cases were serologically confirmed, while C. burnetii was isolated from three human and two animal samples. The human incidence rate was estimated at 1.2 per 100,000 population per year. CONCLUSION: A small number of confirmed clinical cases of Q fever were observed despite the high seroprevalence for C. burnetii in human and animal population of Cyprus. Most of the cases in the local population of Cyprus appear to be subclinical. Moreover further studies should investigate the role of ticks in the epidemiology of Q fever and their relation to human seropositivity.

Methodological aspects of a GIS-based environmental health inspection program used in the Athens 2004 Olympic and Para Olympic Games.

BACKGROUND: The use of geographical information system (GIS) technologies in public health surveillance is gradually gaining momentum around the world and many applications have already been reported in the literature. In this study, GIS technology was used to help county departments of Public Health to implement environmental health surveillance for the Athens 2004 Olympic and Para Olympic Games. METHODS: In order to assess the workload in each Olympic county, 19 registry forms and 17 standardized inspection forms were developed to register and inspect environmental health items requiring inspection (Hotels, restaurants, swimming pools, water supply system etc), respectively. Furthermore, related databases were created using Epi Info 2002 and a geographical information system (GIS) were used to implement an integrated Environmental Health inspection program. The project was conducted in Athens by the Olympic Planning Unit (OPU) of the National School of Public Health, in close cooperation with the Ministry of Health and Social Solidarity and the corresponding departments of Public Health in all municipalities that were scheduled to host events during the Athens 2004 Olympic and Para Olympic games. RESULTS: A total of 44,741 premises of environmental health interest were geocoded into GIS databases and several electronic maps were developed. Using such maps in association with specific criteria, we first identified the maximum workload required to execute environmental health inspections in all premises within the eleven Olympic County Departments of Public Health. Six different scenarios were created for each county, based on devised algorithms in order to design the most effective and realistic inspection program using the available inspectors from each municipality. Furthermore, GIS applications were used to organize the daily inspection program for the Olympic games, provide coloured displays of the inspection results and link those results with the public health surveillance of specific cases or outbreak investigation. CONCLUSION: Our computerised program exhibited significant efficiency in facilitating the prudent use of public health resources in implementing environmental health inspections in densely populated urban areas as well as in rural counties. Furthermore, the application of simple algorithms in integrating human and other resources provided tailored and cost-effective applications to different public health agencies.

Mass gathering preparedness: the experience of the Athens 2004 Olympic and Para-Olympic Games.

Planning for environmental health management of the Athens 2004 Olympic Games included assessment of the capacity and deficiencies of relevant public health agencies in Athens and the other four Olympic cities with 17 detailed questionnaires. Different estimates of the expected number of visitors were made on the basis of experience from previous Olympic Games. Potential public health risks were identified and prioritized. A number of deficiencies in personnel, resources, training, and coordination were identified in most agencies. One hundred and ninety-six environmental health inspectors were expected to work during the Olympic period. Around 18,000 athletes and escorts from 201 countries were expected to participate in the Olympic Games and 7,000 to participate in the Para-Olympic Games. Three different scenarios regarding the number of expected visitors were explored; the most probable estimate being 1,950,000 visitors. Foodborne diseases, waterborne diseases, and heat-related illnesses were considered of high priority during the Olympic period, as were traffic accidents. The Olympic Games are a difficult assignment that demands extensive planning, appropriate resources, and timely reporting and coordination among the various public health agencies.

Mycobacterium tuberculosis transmission among high school students in Greece.

BACKGROUND: The aim of this study was to investigate the requirements and practical steps for screening of Mycobacterium tuberculosis (MTB) transmission among high school student populations in two regional high schools of central Greece. Case-matched control populations from other regional schools were included. METHODS: Case study of two indexed cases, 61 close contacts, 212 casual contacts and 369 controls were investigated. Detailed questionnaires, tuberculin-skin test (PPD test), chest radiography, medical evaluation and DNA fingerprinting of sputum isolates were used. RESULTS: In case A, three (1.97%) of 152 close and casual contacts developed tuberculosis, and a further 25 (16.4%) were classified as infected. In contrast, none of the 121 close or casual contacts investigated for Case B developed tuberculosis or were classified as infected. None of the control populations contained infected individuals. Contacts of case A had a much higher risk (3.08 < RR = 22.29 < 161.69, P < 0.001) of being infected than contacts of case B. Two different strains of MTB were found responsible for these outbreaks. CONCLUSION: There was a considerable difference in the infectivity of the two cases presumably due to environmental and clinical factors, although two different MTB strains were responsible. It is proposed that the extent of case investigation should be individualized with particular emphasis placed among close contacts.