Occurrence Of Secondary Infections Research Articles

Iontophoresis use for increasing drug penetration into root canals and dentinal tubules: A proof-of-concept study

IntroductionThe success of endodontic treatment depends on the significant disinfection of the root canal system, its irregularities, and dentinal tubules. However, achieving complete disinfection remains challenging, with frequent failures and occurrence of secondary infections. Here, we propose using iontophoresis to increase the penetration and distribution of disinfecting agents into root canals, using methylene blue for proof-of-concept. MethodsThe marker was applied in bovine root canals, and the radial distribution of the dye in the dentinal tubules was evaluated by optical microscopy. Iontophoresis was applied at 0.5 and 1.5 mA for 5 and 15 min. ResultsA significant statistical difference (p < 0.05) was observed in the marker penetration between passive and iontophoretic applications. Both current density and application time had an important effect on methylene blue distribution, with a greater efficacy delivery to the apical region achieved after 1.5 mA for 5 min or 0.5 mA for 15 min, showing longer application time can compensate for lower application current. ConclusionIontophoresis increases the penetration and distribution of methylene blue into bovine root canals and dentinal tubules, including its innermost portions. Clinical significanceIontophoresis has shown to be a promising technique for root canal and dentinal tubule disinfection.

Case Report: Intercurrent infections in COVID-19-induced sustained immunodepression: is interferon gamma a suitable drug?

Acute immuno-depression syndrome (AIDs) had been observed in many life-threatening conditions leading to the Intensive Care Unit. and is associated with recurrent secondary infections. We report one COVID-19 patient with a severe ARDS, demonstrating acute immunodepression syndrome lasting for several weeks. The occurrence of secondary infections despite long treatment by antibiotics led to combined interferon γ (IFNγ) as reported previously. The response to IFNγ was evaluated by the flowcytometry HLA-DR expression on circulating monocytes, which was repeated from time to time. The severe COVID-19 patients responded well to IFNγ without adverse events.

Artificial Intelligence: A Next-Level Approach in Confronting the COVID-19 Pandemic.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which caused coronavirus diseases (COVID-19) in late 2019 in China created a devastating economical loss and loss of human lives. To date, 11 variants have been identified with minimum to maximum severity of infection and surges in cases. Bacterial co-infection/secondary infection is identified during viral respiratory infection, which is a vital reason for morbidity and mortality. The occurrence of secondary infections is an additional burden to the healthcare system; therefore, the quick diagnosis of both COVID-19 and secondary infections will reduce work pressure on healthcare workers. Therefore, well-established support from Artificial Intelligence (AI) could reduce the stress in healthcare and even help in creating novel products to defend against the coronavirus. AI is one of the rapidly growing fields with numerous applications for the healthcare sector. The present review aims to access the recent literature on the role of AI and how its subfamily machine learning (ML) and deep learning (DL) are used to curb the pandemic's effects. We discuss the role of AI in COVID-19 infections, the detection of secondary infections, technology-assisted protection from COVID-19, global laws and regulations on AI, and the impact of the pandemic on public life.

Post-COVID-19-Invasive Pulmonary Mycosis

COVID-19 has been associated with myriad manifestations as well as adverse outcomes. One of the less commonly reported consequences of COVID-19 is the occurrence of secondary infections in patients suffering acutely from COVID-19 or in those recuperating. Secondary invasive fungal infections (IFIs) have also been observed earlier in other viral infections such as influenza, parainfluenza, and respiratory syncytial virus infections. Severe lung damage and immunologic derangement resulting from SARS-CoV-2 infection predispose to superinfections. Risk factors for secondary IFI includes immunologic derangement and immunoparalysis resulting from SARS-CoV-2 infection, neutropenia, or lymphopenia, poorly controlled diabetes, structural lung disease fungal colonization, and drugs such as corticosteroids or immunomodulators given as therapies for COVID-19. Invasive aspergillosis following COVID-19 is most commonly described fungal infection but other non-Aspergillus fungal infections (including mucormycosis) has also been reported. Herein we describe two interesting cases of secondary infections developing in patients beyond the acute phase of COVID-19 who had similar presentations but with different diagnoses and requiring different management strategies. Patient in case 1 developed COVID-19-associated subacute invasive pulmonary aspergillosis (SAIA) and patient in case 2 had COVID-19 associated pulmonary mucormycosis (CAPM). We have also described the various postulated immune-pathogenesis of the super-added fungal infections in COVID-19 patients.

Dexamethasone and tocilizumab treatment considerably reduces the value of C-reactive protein and procalcitonin to detect secondary bacterial infections in COVID-19 patients

BackgroundProcalcitonin (PCT) and C-reactive protein (CRP) were previously shown to have value for the detection of secondary infections in critically ill COVID-19 patients. However, since the introduction of immunomodulatory therapy, the value of these biomarkers is unclear. We investigated PCT and CRP kinetics in critically ill COVID-19 patients treated with dexamethasone with or without tocilizumab, and assessed the value of these biomarkers to detect secondary bacterial infections.MethodsIn this prospective study, 190 critically ill COVID-19 patients were divided into three treatment groups: no dexamethasone, no tocilizumab (D−T−), dexamethasone, no tocilizumab (D+T−), and dexamethasone and tocilizumab (D+T+). Serial data of PCT and CRP were aligned on the last day of dexamethasone treatment, and kinetics of these biomarkers were analyzed between 6 days prior to cessation of dexamethasone and 10 days afterwards. Furthermore, the D+T− and D+T+ groups were subdivided into secondary infection and no-secondary infection groups to analyze differences in PCT and CRP kinetics and calculate detection accuracy of these biomarkers for the occurrence of a secondary infection.ResultsFollowing cessation of dexamethasone, there was a rebound in PCT and CRP levels, most pronounced in the D+T− group. Upon occurrence of a secondary infection, no significant increase in PCT and CRP levels was observed in the D+T− group (p = 0.052 and p = 0.08, respectively). Although PCT levels increased significantly in patients of the D+T+ group who developed a secondary infection (p = 0.0003), this rise was only apparent from day 2 post-infection onwards. CRP levels remained suppressed in the D+T+ group. Receiver operating curve analysis of PCT and CRP levels yielded area under the curves of 0.52 and 0.55, respectively, which are both markedly lower than those found in the group of COVID-19 patients not treated with immunomodulatory drugs (0.80 and 0.76, respectively, with p values for differences between groups of 0.001 and 0.02, respectively).ConclusionsCessation of dexamethasone in critically ill COVID-19 patients results in a rebound increase in PCT and CRP levels unrelated to the occurrence of secondary bacterial infections. Furthermore, immunomodulatory treatment with dexamethasone and tocilizumab considerably reduces the value of PCT and CRP for detection of secondary infections in COVID-19 patients.

Myeloid phenotypes in severe COVID-19 predict secondary infection and mortality: a pilot study

BackgroundDe-regulated host response to severe coronavirus disease 2019 (COVID-19), directly referring to the concept of sepsis-associated immunological dysregulation, seems to be a strong signature of severe COVID-19. Myeloid cells phenotyping is well recognized to diagnose critical illness-induced immunodepression in sepsis and has not been well characterized in COVID-19. The aim of this study is to review phenotypic characteristics of myeloid cells and evaluate their relations with the occurrence of secondary infection and mortality in patients with COVID-19 admitted in an intensive care unit.MethodsRetrospective analysis of the circulating myeloid cells phenotypes of adult COVID-19 critically ill patients. Phenotyping circulating immune cells was performed by flow cytometry daily for routine analysis and twice weekly for lymphocytes and monocytes subpopulations analysis, as well as monocyte human leukocyte antigen (mHLA)-DR expression.ResultsOut of the 29 critically ill adult patients with severe COVID-19 analyzed, 12 (41.4%) developed secondary infection and six patients died during their stay. Monocyte HLA-DR kinetics was significantly different between patients developing secondary infection and those without, respectively, at day 5–7 and 8–10 following admission. The monocytes myeloid-derived suppressor cells to total monocytes ratio was associated with 28- and 60-day mortality. Those myeloid characteristics suggest three phenotypes: hyperactivated monocyte/macrophage is significantly associated with mortality, whereas persistent immunodepression is associated with secondary infection occurrence compared to transient immunodepression.ConclusionsMyeloid phenotypes of critically ill COVID-19 patients may be associated with development of secondary infection, 28- and 60-day mortality.

Combination therapy with tocilizumab and corticosteroids for aged patients with severe COVID-19 pneumonia: A single-center retrospective study

BackgroundThe role of combination immunomodulatory therapy with systemic corticosteroids and tocilizumab (TCZ) for aged patients with COVID-19-associated cytokine release syndrome remains unclear. MethodsA retrospective single-center study was conducted on consecutive patients aged ≥65 years who developed severe COVID-19 between 03 March and 01 May 2020 and were treated with corticosteroids at various doses (methylprednisolone 0.5mg/kg/12h to 250mg/24h), either alone (CS group) or associated with intravenous tocilizumab (400–600mg, one to three doses) (CS-TCZ group). The primary outcome was all-cause mortality by day +14, whereas secondary outcomes included mortality by day +28 and clinical improvement (discharge and/or a ≥2 point decrease on a 6-point ordinal scale) by day +14. Propensity score (PS)-based adjustment and inverse probability of treatment weights (IPTW) were applied. ResultsTotals of 181 and 80 patients were included in the CS and CS-TCZ groups, respectively. All-cause 14-day mortality was lower in the CS-TCZ group, both in the PS-adjusted (hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.17–0.68; P=0.002) and IPTW-weighted models (odds ratio [OR]: 0.38; 95% CI: 0.21–0.68; P=0.001). This protective effect was also observed for 28-day mortality (PS-adjusted HR: 0.38; 95% CI: 0.21–0.72; P=0.003). Clinical improvement by day +14 was higher in the CS-TCZ group with IPTW analysis only (OR: 2.26; 95% CI: 1.49–3.41; P<0.001). The occurrence of secondary infection was similar between both groups. ConclusionsThe combination of corticosteroids and TCZ was associated with better outcomes among patients aged ≥65 years with severe COVID-19.

Decreased Human Leukocyte Antigen DR on Circulating Monocytes Expression After Severe Pediatric Trauma: An Exploratory Report.

Major trauma in adults induces immune dysfunction, with diminished expression of human leukocyte antigen-DR on circulating monocytes. No pediatric data are available. This study described the kinetics of human leukocyte antigen-DR on circulating monocytes following major pediatric trauma and relationships between human leukocyte antigen-DR on circulating monocytes and outcomes. Prospective observational study. PICU and trauma unit at a tertiary-care university hospital in South Africa. Children between 1 month and 13 years hospitalized for severe brain trauma or trauma with an Injury Severity Score greater than or equal to 16, from November 2016 to March 2017. None. We included 36 children. Median (interquartile range) age and Injury Severity Score were 7 years (4.9-10.5 yr) and 25 years (22.7-30 yr), respectively. Blood samples (n = 83) for standardized human leukocyte antigen-DR on circulating monocytes measurement were collected at days 1-2, 3-4, and 8-9 after injury (D1, D3, and D8, respectively). On D1, median (interquartile range) human leukocyte antigen-DR on circulating monocytes was markedly reduced relative to normal values (7,031 [5,204-11,201] antibodies per cell). There was a significant increase in human leukocyte antigen-DR on circulating monocytes from D1 to D8. Although all patients with secondary infections (n = 8; 22%) had human leukocyte antigen-DR on circulating monocytes less than 15,000 antibodies per cell at D3, human leukocyte antigen-DR on circulating monocytes levels were not associated with the occurrence of secondary infections (p = 0.22). At D3, human leukocyte antigen-DR on circulating monocytes was significantly higher in patients discharged home (n = 21) by Day 30 after trauma compared with those who died or were still hospitalized (n = 14) (p = 0.02). Pediatric severe trauma induced an early and dramatic decrease in human leukocyte antigen-DR on circulating monocytes expression. This alteration of innate immunity was not associated with the occurrence of secondary infection, possibly due to a lack of statistical power. However, human leukocyte antigen-DR on circulating monocytes at Day 3 is a potential indicator of those at high risk of secondary infection and worse outcomes.

Imbalance of Circulating Innate Lymphoid Cell Subpopulations in Patients With Septic Shock.

Background: Septic shock, a major cause of death in critical care, is the clinical translation of a cytokine storm in response to infection. It can be complicated by sepsis-induced immunosuppression, exemplified by blood lymphopenia, an excess of circulating Treg lymphocytes, and decreased HLA-DR expression on circulating monocytes. Such immunosuppression is associated with secondary infections, and higher mortality. The effect of these biological modifications on circulating innate lymphoid cells (ILCs) has been little studied.Methods: We prospectively enrolled patients with septic shock (Sepsis-3 definition) in the intensive care unit (ICU) of Timone CHU Hospital. ICU controls (trauma, cardiac arrest, neurological dysfunction) were recruited at the same time (NCT03297203). We performed immunophenotyping of adaptive lymphocytes (CD3+ T cells, CD19+ B cells, CD4+CD25+FoxP3+ Treg lymphocytes), ILCs (CD3−CD56+ NK cells and helper ILCs – ILC1, ILC2, and ILC3), and monocytes by flow cytometry on fresh blood samples collected between 24 and 72 h after admission.Results: We investigated adaptive and innate circulating lymphoid cells in the peripheral blood of 18 patients in septic shock, 15 ICU controls, and 30 healthy subjects. As expected, the peripheral blood lymphocytes of all ICU patients showed lymphopenia, which was not specific to sepsis, whereas those of the healthy volunteers did not. Circulating CD3+ T cells and CD3−CD56+ NK cells were mainly concerned. There was a tendency toward fewer Treg lymphocytes and lower HLA-DR expression on monocytes in ICU patients with sepsis. Although the ILC1 count was higher in septic patients than healthy subjects, ILC2, and ILC3 counts were lower in both ICU groups. However, ILC3s within the total ILCs were overrepresented in patients with septic shock. The depression of immune responses has been correlated with the occurrence of secondary infections. We did not find any differences in ILC distribution according to this criterion.Conclusion: All ICU patients exhibit lymphopenia, regardless of the nature (septic or sterile) of the initial medical condition. Specific distribution of circulating ILCs, with an excess of ILC1, and a lack of ILC3, may characterize septic shock during the first 3 days of the disease.

30 years of dengue fatal cases in Brazil: a laboratorial-based investigation of 1047 cases

BackgroundDengue viruses (DENV) have emerged and reemerged in Brazil in the past 30 years causing explosive epidemics. The disease may range from clinically asymptomatic infections to severe and fatal outcomes. We aimed to describe the epidemiological, clinical and laboratorial aspects of the dengue fatal cases received by a Regional Reference Laboratory, Brazil in 30 years.MethodsA total of 1047 suspected fatal dengue cases were received from 1986 to 2015 and analyzed in the Laboratory of Flavivirus, FIOCRUZ. Suspected cases were submitted to viral detection, serological and molecular methods for cases confirmation. Influence of gender, age, serotype and type of infection (primary/secondary) on death outcome, as well the interactions between serotype and age or infection and age and type of infection were also studied.ResultsA total of 359 cases (34.2%) were confirmed and DENV-1 (11.1%), DENV-2 (43.9%), DENV-3 (32.8%) and DENV-4 (13.7%) were detected. Overall, fatal cases occurred more often in primary infections (59.3%, p = 0.001). However, in 2008, fatal cases were mainly associated to secondary infections (p = 0.003). In 2008 and 2011, deaths were more frequent on children and those infected by DENV-2 presented a higher risk for fatal outcome. Moreover, children with secondary infections had a 4-fold higher risk for death.ConclusionsDengue is a multifactorial disease and, factors such as viral strain/serotype, occurrence of secondary infections and co-morbidities may lead to a severe outcome. However, the high dengue incidence and transmission during epidemics, such as those observed in Brazil may overwhelm and collapse the public health services, potentially impacting on increased disease severity and mortality.

Dengue type 4 in Rio de Janeiro, Brazil: case characterization following its introduction in an endemic region

BackgroundDue to the populations’ susceptibility, DENV-4 introduction in 2010 led to the occurrence of explosive epidemics in the following years in Brazil. In 2011, DENV-4 was identified in Rio de Janeiro (RJ) and it was prevalent in 2012 and 2013. Here, we aimed to characterize clinical, epidemiological and laboratorial aspects of DENV-4 cases after this serotype introduction in an endemic scenario.MethodsDengue suspected cases (n = 3727) were received and analyzed from January 2011 to December 2013, during outbreaks occurred in RJ, Brazil. Samples were submitted to virological, serological and molecular methods for case confirmation. DENV-4 cases (n = 705) were characterized according to the type of infection, disease severity and, viremia levels and NS1 antigenemia were accessed. Representative strains were partial sequenced for genotyping.ResultsDENV-4 was identified in 44.2% (705/1593) of dengue positive cases, virus isolated in 48.7% of the cases. Anti-DENV IgM was detected in 39.4% of the cases, however an increased detection was observed in cases with ≥4 days of symptoms (57.0%). NS1 antigen was identified in 41.5% of DENV-4 cases however, after immune complexes dissociation, the detection significantly increased (87.6%). Females were more affected than males, so did children aged 11–15 years old. Primary cases were more frequently observed than secondary ones and most of them were classified as dengue. No differences on NS1 antigenemia and viraemia within the groups were observed. Despite the higher frequency of severe disease on individuals >65 years old, no differences were observed among the groups and type of infection. However, DENV-4 fatal cases were more frequent on secondary infections (57.1%). DENV-4 Genotype II was identified with a probable origin from Venezuela and Colombia.ConclusionsIt has been shown that laboratorial diagnosis is still a reliable tool for the disease surveillance, detecting and confirming emerging epidemics. Despite the occurrence of secondary infections, most DENV-4 cases presented a mild disease. As RJ is endemic for dengue, high rates of secondary infections would be expected. Despite the existence of two genotypes, only Genotype II was identified in our study.

Dengue epidemics in two distinct periods reveal distinct epidemiological, laboratorial and clinical aspects in a same scenario: analysis of the 2010 and 2013 epidemics in Mato Grosso do Sul, Brazil.

Dengue is a major problem in Brazil. Epidemiological and clinical aspects were characterized in patients from two epidemics which occurred in Mato Grosso do Sul, Brazil. Dengue cases were classified according to the 2009 WHO criteria, tested by serological and molecular biology tests and analysed for nonstructural protein 1 (NS1) antigenemia. Dengue was confirmed in 78.7% (48/61) and 75.6% (118/156) of the cases studied in 2010 and 2013, respectively. DENV-1 and DENV-2 were the serotypes involved in the 2010 epidemic and DENV-4 in the 2013 one. Most of the cases were classified as dengue without warning; however, severe dengue was observed in 18.7% (9/48) of the cases in 2010 and less observed in DENV-4 cases. NS1 levels were higher in patients with dengue with warning signs and severe dengue in 2010. Circulating aspartate aminotransferase (AST) and alanine transferase (ALT) were altered in all groups, independently of the infecting serotype or epidemic. Patients with DENV-1 and DENV-2 presented significant lower monocyte counts when compared to patients with DENV-4. An inverse correlation was found between platelet count, leucocytes, monocytes and NS1 levels. Epidemics caused by the prevalence of distinct DENV serotypes had different impacts and clinical characteristics in a same scenario and, despite the occurrence of secondary infections, the DENV-4 emergence was not associated with severe cases.

Mechanical ventilation in patients with most severe forms of influenza a H1N1

Pandemic of A H1N1 influenza is noted for its rapid spreading and life-threatening consequences like acute respiratory distress syndrome (ARDS) which requires mechanical ventilation (MV) and intensive therapy (IT).The aim of the study was to determine the significance of mechanical ventilation application in the presence of comorbidities on the outcome of the disease and patients with severe forms of acute influenza caused by A H1N1 virus. Five patients with acute respiratory failure caused by A H1N1 influenza that required MV were included in the study. Course and outcome of the treatment were monitored in relation to age and sex of the patients, concomitant diseases, time of influenza beginning, a time of admittance in an intensive care unit, a time of an endotracheal intubation and MV beginning, MV duration and occurrence of secondary infections. Three patients were on a very prolonged MV (39, 43 and 20 days, respectively) and they all survived. Two patients with a significantly shorter duration of MV (14 and 12 days, respectively) died because of a very severe clinical course and concomitant diseases. Unexpectedly, we found a positive correlation between duration of MV and survival although two patients, who were on MV for the longest period of time (43 and 39 days, respectively), developed, as a complication, secondary bacterial pneumonia. Intensive therapy of patients with ARDS due to A H1N1 influenza virus requires MV which should be carried out according to guidelines of international expert forums. That is in accordance with our unexpected observation on negative correlation between duration of MV and fatal outcome. Intensive treatment of these patients, specially MV, can be very prolonged and, therefore, requires specialized teams of anesthesiologists, separate, isolated intensive therapy units and high level of medical staff protection, as was the case in this study, so no member of medical staff was infected.

Diagnosis of mycotoxicoses in veterinary medicine

The problem of mycotoxin presence in animal feed and the consequences that arise due to this, represent a great challenge for anyone encountering them. In the chain which includes studies from prevention to treatment, a very important place and a frequent source of confusion is the process of diagnosing diseases caused by mycotoxins. The aim of this paper is to present a long experience of the team of experts at the Institute of Veterinary Medicine of Serbia in Belgrade, who follows this issue in terms of clinical manifestations of mycotoxicoses in different animal species, pathomorphological and pathohistological changes that characterize them, and laboratory analysis of feed which is the source of those biological hazards and natural contaminants. Based on the findings it could be concluded that mycotoxin contamination is common. Although these levels usually do not exceed the limits laid by the legislation, considering the cumulative effects and possible chronic exposure of animals to their harmful influence, appropriate and competent approach is necessary. Namely, even when direct losses, such as animals? mortality, are not present, indirect losses, due to a drop of animal performances and production, as well as the occurrence of secondary infections, should not be neglected.

Plant-Parasitic Nematodes Infecting Grapevine in Southern Spain and Susceptible Reaction to Root-Knot Nematodes of Rootstocks Reported as Moderately Resistant.

Incidence and nematode population densities of plant-parasitic nematodes were determined in 64 samples of soil and grapevine roots collected from commercial vineyards in southern Spain between October 2003 and May 2005. In addition, a histopathological study was done of root-stock roots naturally infected by root-knot nematodes (Meloidogyne spp.). Nematodes infecting the rootstocks were identified according to conventional procedures, and the Meloidogyne spp. were furthermore identified by sequence characterized amplified region-polymerase chain reaction (SCAR-PCR) and isozyme esterase analyses. The most important plant-parasitic nematodes detected, in order of decreasing frequency of total soil infestation and root infection (percentage of samples), were Mesocriconema xenoplax (34.4%), Meloidogyne incognita (26.6%), Meloidogyne javanica (14.1%), Xiphinema index (12.5%), Xiphinema italiae (10.9%), Pratylenchus vulnus (6.3%), and Meloidogyne arenaria (1.6%). No disease symptoms were observed on aboveground plant parts of the infected grapevines, except for plants in some fields where soil was infested with the virus-vector nematodes X. index and X. italiae. Those grapevines showed a yellow mosaic pattern in leaves early in the growing season and the internode shortening characteristic of infections by Grapevine fanleaf virus. Rootstocks infected by root-knot nematodes (Meloidogyne spp.) showed distorted feeder roots and large- to moderate-sized root galls, present either singly or in clusters. Histopathology of galled roots showed a typical susceptible response to infection by root-knot nematodes: cellular alterations were induced in the cortex, endodermis, pericycle, and vascular system, including giant-cell formation and severe distortion of vascular tissues. Most Meloidogyne egg masses ocurred on the surface of the galled root tissues, a position that could facilitate dispersion of the nematode eggs and juveniles and the occurrence of secondary infections. Some of the grapevine rootstocks surveyed in this study (Paulsen 1103, Richter 110, Rupestris du Lot, and SO4) had previously been reported to be resistant to Meloidogyne spp.; however, the population densities of these nematodes found in soil and roots sampled in the present study, as well as the compatible host-parasite relationship revealed by histopathology, indicate a susceptible response to Meloidogyne spp. from southern Spain.

Modélisation de cinétiques de la maladie de la tache de la carotte provoquée par un complexe d'agents pathogènes du genre Pythium dominé par le Pythium violae

Carrot cavity spot is caused by a complex of pathogens belonging to the genus Pythium, including Pythium violae. The disease is characterized by the appearance of sunken elliptical lesions on the taproot. The objective of the present study is to identify, understand, and prioritize the processes that induce the spatio-temporal kinetics of epidemics of cavity spot. We favoured the hypothesis that considers primary infection (from soilborne inoculum) and secondary infection (root-to-root contaminations from existing lesions, i.e., auto- and allo-infections). Epidemics were obtained during a 3-year field experiment after artificial soil infestation of plots with P. violae at increasing inoculum doses. Different kinetics of cavity spot were described using standardized disease measurements. The analysis of the incidence curves showed the early appearance of a plateau, with differences in the disease level that are positively correlated with the inoculum doses. These differences disappeared at the end of the cropping season. Three simulation models, integrating or not the concomitance of the primary and secondary infections, were fitted to the disease incidence to test if progress curves were compatible with the hypothesis of the occurrence of both infection processes: the logistic model, the bilogistic model of Hau and Amorim, and the model of Brassett and Gilligan without temporal decline of the soil inoculum potential. The quality of the fitting was correct in the three cases, and the hypothesis of the occurrence of secondary infections was not refuted. This result is an important argument to demonstrate the polycyclic nature of the disease.

Temporal Clusters of Salmonella Serovars in Humans in Alberta, 1990–2001

Temporal clusters of salmonellosis are believed to occur but have not been quantitatively explored, thus, our objectives were to describe trends, seasonal patterns, and clusters of salmonellosis in humans in Alberta by examining isolates reported through passive surveillance systems. Cases of salmonellosis reported through Notifiable Disease Records between January 1990 and December 2001 were obtained from Alberta Health and Wellness. Least squares regression was used to characterize the distribution (long-term trends and seasonal patterns) of isolates. A cluster detection test was used to determine if and when isolates of specific serovars aggregated in time, over and above the background distribution. Comparisons were made to temporal patterns in Alberta livestock and to known outbreaks in humans. S. Typhimurium, Enteritidis, Hadar, Heidelberg, and Thompson were the five most common serovars of the 9,188 isolates reported. The annual number of isolates was relatively stable over time, with a distinct summertime seasonal pattern. Clusters were observed in 23 of 32 serovars examined. More clusters occurred in September and October than in other months, and in 1998 through 2001 than in the early to mid-1990s. Also, more clusters were of short duration than long. Short-duration clusters likely indicate a point source of infection, while long-duration clusters may indicate exposure to a persistent common source or the occurrence of secondary infections. A sharp increasing trend and a large cluster of S. Heidelberg may have public health implications. Surveillance activities focussed on similarities between common serovars, trends, and temporal clusters in humans and animals, and studies on factors associated with autumn clusters may be useful in preventing outbreaks in humans.

Stress-dose corticosteroid therapy for sepsis and acute lung injury or acute respiratory distress syndrome in critically ill adults.

Sepsis and acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) are associated with high mortality rates despite recent therapeutic advances. Both disease states involve uncontrolled host defense responses that lead to inflammation, endothelial damage, enhanced coagulation, diminished fibrinolysis and fibroproliferation to produce microthrombi, and relative adrenal insufficiency. Corticosteroids inhibit the host defense response and may offer an inexpensive therapeutic option. Results of several randomized, double-blind studies demonstrated no survival benefit and higher secondary infection rates when supraphysiologic doses of corticosteroids were administered for less than 24 hours. Recently, the emphasis of research for corticosteroid therapy has involved adrenocortical replacement dosage regimens administered for several days to weeks, with doses corresponding to the stress level of the disease. Stress-dose therapy with hydrocortisone in patients with septic shock who require vasopressor support, especially if adrenal insufficiency is present, accelerates hemodynamic stability and reduces mortality. The frequency of gastrointestinal hemorrhage was higher with corticosteroid therapy than with placebo, but the occurrence of secondary infections was similar to that of placebo. The only randomized, double-blind study that evaluated stress-dose methylprednisolone therapy for ARDS was terminated early after only 24 patients were enrolled because therapy with methylprednisolone was associated with enhanced survival despite higher secondary infection rates. A multicenter study investigating stress-dose methylprednisolone for ARDS is under way and should provide valuable information. Sufficient data support stress-dose hydrocortisone therapy for vasopressor-dependent septic shock. Stress-dose methylprednisolone therapy for ALI-ARDS requires further study but may be warranted in cases of refractory infection-induced ARDS when impending mortality is likely.

Aetiology, outcome and prognostic factors in community-acquired pneumonia requiring hospitalization

Outcome and prognostic factors were prospectively studied in 277 adult patients (average age 62 yrs) with community-acquired pneumonia requiring hospitalization. The aetiology was established in 68%, with S. pneumoniae as the predominating agent. Mortality was 4% (12 of 277), and all but one who died were greater than or equal to 60 yrs of age. Features associated with high mortality included greater age, absence of chills and chest pain, high respiratory rate (greater than 30 breaths.min-1) and low serum albumin on admission, and the occurrence of airway colonization and secondary infection during hospital stay. Multivariate analysis showed that low serum albumin and the occurrence of secondary infection, but also absence of chills and airway colonization, were correlated to a higher mortality. In patients who survived, the median length of hospital stay was seven days, and at follow-up, about eight weeks after admission, 81% had recovered and chest X-ray was normal in 84%. In conclusion, we believe that the outcome of community-acquired pneumonia can be influenced by prophylactic measures against pneumococcal infection, and an increased surveillance of risk patients.

Occult Infected Fracture of the Femur

The unusual occurrence of secondary infection of a closed fracture in two patients is described. The various possible etiologies of this syndrome and alternatives for treatment are discussed. Recognition of this entity and initiation of early definitive care, usually including open packing of the fracture wound, are emphasized.