Secondary Infection Risk Research Articles

Incidence of Secondary Bacterial Infections Following Utilization of Tocilizumab for the Treatment of COVID-19 - A Matched Retrospective Cohort Study.

Introduction:Immunosuppressive agents are theorized to target the cytokine storm syndrome in COVID-19. However, the downstream effects regarding susceptibilities to secondary infection risk remains unknown. This study seeks to determine risk differences for secondary infections among COVID-19 patients who did and did not receive tocilizumab.Methods:We conducted a matched retrospective cohort study from two large, acute care hospitals in Western Connecticut from March 1, to May 31, 2020. We collected variables using manual medical record abstraction. The primary exposure variable was any dose of tocilizumab. The primary outcome was any healthcare-associated bacterial or fungal infection as defined by the National Healthcare Safety Network. We performed a Kaplan–Meier analysis to assess the crude difference in cumulative probability of healthcare-associated infection (HAI) across exposure groups. We also performed a multivariable Cox regression analysis to determine the hazard ratio for HAI by exposure group while controlling for potential confounders.Results:The Kaplan–Meier analysis demonstrated no difference in the cumulative probability of HAI across groups. The adjusted hazard of HAI for patients given tocilizumab was 0.85 times that of patients not given tocilizumab (95% confidence interval = 0.29, 2.52, P = 0.780) after controlling for relevant confounders.Conclusions:Tocilizumab did not increase the incidence of secondary infection among COVID-19 patients. Larger, randomized trials should evaluate infection as a secondary outcome to validate this finding.

Estimating and interpreting secondary attack risk: Binomial considered biased

The household secondary attack risk (SAR), often called the secondary attack rate or secondary infection risk, is the probability of infectious contact from an infectious household member A to a given household member B, where we define infectious contact to be a contact sufficient to infect B if he or she is susceptible. Estimation of the SAR is an important part of understanding and controlling the transmission of infectious diseases. In practice, it is most often estimated using binomial models such as logistic regression, which implicitly attribute all secondary infections in a household to the primary case. In the simplest case, the number of secondary infections in a household with m susceptibles and a single primary case is modeled as a binomial(m, p) random variable where p is the SAR. Although it has long been understood that transmission within households is not binomial, it is thought that multiple generations of transmission can be neglected safely when p is small. We use probability generating functions and simulations to show that this is a mistake. The proportion of susceptible household members infected can be substantially larger than the SAR even when p is small. As a result, binomial estimates of the SAR are biased upward and their confidence intervals have poor coverage probabilities even if adjusted for clustering. Accurate point and interval estimates of the SAR can be obtained using longitudinal chain binomial models or pairwise survival analysis, which account for multiple generations of transmission within households, the ongoing risk of infection from outside the household, and incomplete follow-up. We illustrate the practical implications of these results in an analysis of household surveillance data collected by the Los Angeles County Department of Public Health during the 2009 influenza A (H1N1) pandemic.

A Longitudinal Study of SARS-CoV-2 Secondary Infection Risks in Family Members: Psychosocial Factors May be More Important than Biological Ones

A Longitudinal Study of SARS-CoV-2 Secondary Infection Risks in Family Members: Psychosocial Factors May be More Important than Biological Ones

Current Evidence of Interleukin-6 Signaling Inhibitors in Patients With COVID-19: A Systematic Review and Meta-Analysis.

Background: Interleukin-6 (IL-6) is known to be detrimental in coronavirus disease 2019 (COVID-19) because of its involvement in driving cytokine storm. This systematic review and meta-analysis aimed to assess the safety and efficacy of anti-IL-6 signaling (anti-IL6/IL-6R/JAK) agents on COVID-19 based on the current evidence. Methods: Studies were identified through systematic searches of PubMed, EMBASE, ISI Web of Science, Cochrane library, ongoing clinical trial registries (clinicaltrials.gov), and preprint servers (medRxiv, ChinaXiv) on August 10, 2020, as well as eligibility checks according to predefined selection criteria. Statistical analysis was performed using Review Manager (version 5.3) and STATA 12.0. Results: Thirty-one studies were included in the pooled analysis of mortality, and 12 studies were identified for the analysis of risk of secondary infections. For mortality analysis, 5630 COVID-19 cases including 2,132 treated patients and 3,498 controls were analyzed. Anti-IL-6 signaling agents plus standard of care (SOC) significantly decreased the mortality rate compared to SOC alone (pooled OR = 0.61, 95% CI 0.45–0.84, p = 0.002). For the analysis of secondary infection risk, 1,624 patients with COVID-19 including 639 treated patients and 985 controls were included, showing that anti-IL-6 signaling agents did not increase the rate of secondary infections (pooled OR = 1.21, 95% CI 0.70–2.08, p = 0.50). By contrast, for patients with critical COVID-19 disease, anti-IL-6 signaling agents failed to reduce mortality compared to SOC alone (pooled OR = 0.75, 95% CI 0.42–1.33, p = 0.33), but they tended to increase the risk of secondary infections (pooled OR = 1.85, 95% CI 0.95–3.61, p = 0.07). A blockade of IL-6 signaling failed to reduce the mechanical ventilation rate, ICU admission rate, or elevate the clinical improvement rate. Conclusion: IL-6 signaling inhibitors reduced the mortality rate without increasing secondary infections in patients with COVID-19 based on current studies. For patients with critical disease, IL-6 signaling inhibitors did not exhibit any benefit.

Estimating individual risks of COVID-19-associated hospitalization and death using publicly available data.

We describe a method to estimate individual risks of hospitalization and death attributable to non-household and household transmission of SARS-CoV-2 using available public data on confirmed-case incidence data along with estimates of the clinical fraction, timing of transmission, isolation adherence, secondary infection risks, contact rates, and case-hospitalization and case-fatality ratios. Using the method, we estimate that risks for a 90-day period at the median daily summertime U.S. county confirmed COVID-19 case incidence of 10.8 per 100,000 and pre-pandemic contact rates range from 0.4 to 8.9 per 100,000 for the four deciles of age between 20 and 60 years. The corresponding 90-day period risk of hospitalization ranges from 13.7 to 69.2 per 100,000. Assuming a non-household secondary infection risk of 4% and pre-pandemic contact rates, the share of transmissions attributable to household settings ranges from 73% to 78%. These estimates are sensitive to the parameter assumptions; nevertheless, they are comparable to the COVID-19 hospitalization and fatality rates observed over the time period. We conclude that individual risk of hospitalization and death from SARS-CoV-2 infection is calculable from publicly available data sources. Access to publicly reported infection incidence data by setting and other exposure characteristics along with setting specific estimates of secondary infection risk would allow for more precise individual risk estimation.

Coronavirus Occurrence and Transmission Over 8 Years in the HIVE Cohort of Households in Michigan

BackgroundAs part of the Household Influenza Vaccine Evaluation (HIVE) study, acute respiratory infections (ARI) have been identified in children and adults from 2010 to 2018.MethodsAnnually, 890 to 1441 individuals were followed and contacted weekly to report ARIs. Specimens collected during illness were tested for human coronaviruses (HCoV) types OC43, 229E, HKU1, and NL63.ResultsIn total, 993 HCoV infections were identified during the 8 years, with OC43 most commonly seen and 229E the least. HCoVs were detected in a limited time period, between December and April/May and peaked in January/February. Highest infection frequency was in children <5 years (18 per 100 person-years), with little variation in older age groups (range, 7 to 11 per 100 person-years). Overall, 9% of adult cases and 20% of cases in children were associated with medical consultation. Of the 993 infections, 260 were acquired from an infected household contact. The serial interval between index and household-acquired cases ranged from 3.2 to 3.6 days and the secondary infection risk ranged from 7.2% to 12.6% by type.ConclusionsCoronaviruses are sharply seasonal. They appear, based on serial interval and secondary infection risk, to have similar transmission potential to influenza A(H3N2) in the same population.

Household Transmission of Seasonal Influenza From HIV-Infected and HIV-Uninfected Individuals in South Africa, 2013-2014.

We estimated the household secondary infection risk (SIR) and serial interval (SI) for influenza transmission from HIV-infected and HIV-uninfected index cases. Index cases were the first symptomatic person in a household with influenza-like illness, testing influenza positive on real-time reverse transcription polymerase chain reaction (rRT-PCR). Nasopharyngeal swabs collected from household contacts every 4 days were tested by rRT-PCR. Factors associated with SIR were evaluated using logistic regression. We enrolled 28 HIV-infected and 57 HIV-uninfected index cases. On multivariable analysis, HIV-infected index cases were less likely to transmit influenza to household contacts (odds ratio [OR] 0.2; 95% confidence interval [CI], 0.1-0.6; SIR 16%, 18/113 vs 27%, 59/220). Factors associated with increased SIR included index age group 1-4 years (OR 3.6; 95% CI, 1.2-11.3) and 25-44 years (OR 8.0; 95% CI, 1.8-36.7), and contact age group 1-4 years (OR 3.5; 95% CI, 1.2-10.3) compared to 5-14 years, and sleeping with index case (OR 2.7; 95% CI, 1.3-5.5). HIV infection of index case was not associated with SI. HIV-infection was not associated with SI. Increased infectiousness of HIV-infected individuals is likely not an important driver of community influenza transmission.

Viral DNAemia and Immune Suppression in Pediatric Sepsis.

Demonstrate that DNA viremia is common in pediatric sepsis and quantitate its associations with host immune function and secondary infection risk. Retrospective analysis of a prospective cohort study. Seventy-three children admitted with sepsis-induced organ failure. None. This study was performed as an ancillary investigation to a single-center prospective study of children with severe sepsis. Longitudinally collected, batched, frozen plasma was examined using real time-polymerase chain reaction for the presence of cytomegalovirus, Epstein-Barr virus, herpes simplex virus, human herpes virus-6, torque teno virus, and adenovirus DNA. Innate immune function was also measured longitudinally via quantification of ex vivo lipopolysaccharide -induced tumor necrosis factor-α production capacity. Viral DNAemia with a virus other than torque teno virus was detected in 28 of 73 subjects (38%) and included cytomegalovirus 5%, Epstein-Barr virus 11%, herpes simplex virus 4%, human herpes virus-6 8%, and adenovirus 26%. In addition, torque teno virus was detected in 89%. Epstein-Barr virus DNAemia was associated with preexisting immune suppression (p = 0.007) Viral DNAemia was associated with preexisting immune suppression and high risk for the subsequent development of secondary infection (p < 0.05 for both). Subjects with viral DNAemia had lower innate immune function over time compared with those who were virus negative (p < 0.05). DNAemia from multiple viruses can be detected in septic children and is strongly associated with preexisting immune suppression and secondary infection risk. The role of DNA viruses in the perpetuation of impaired host defense in this setting should be the subject of prospective study.

Therapeutic benefits of glutamine: An umbrella review of meta-analyses.

Glutamine may be an essential amino acid in patients with catabolic disease, as it has been demonstrated that circulating glutamine levels drop during critical illness and following major surgery; this may result in an increase in secondary infection risk, recovery time and mortality rates. However, there is much discrepancy in the literature with regards to randomized controlled studies, and therefore, the present study is an umbrella review of published meta-analyses, conducted to examine the effectiveness of glutamine's role as a therapeutic agent. A search using PubMed, Cochrane Library and CINAHL from January 1st, 1980 to December 31st, 2016 was conducted using the following strategy: 'Glutamine AND (meta-analysis OR systematic review)' and publications were retrieved, which provided quantitative statistical analysis of pooled treatment effects on the relative risks of infectious complications, mortality and length of stay in hospital. A total of 22 meta-analyses were entered into the current umbrella review. As displayed in Tables I, II and III, these analyses are split into three groups, based on different parameters. Of the 19 meta-analyses investigating the effects of infectious complications, 15 identified statistically significant reductions in complications, with relative risks ranging between 0.42 and 0.93. In addition, 12 of the 18 meta-analyses analyzing the length of hospital stays presented statistically significant reductions in the length of stay, with reductions ranging between 0.19 to 4.73 days. Only 4 of the 15 meta-analyses studying mortality effects identified statistically significant reductions in mortality with relative risks ranging between 0.64 and 1.28. Statistically significant heterogeneity was observed in 16 of 22 meta-analyses, and publication bias was observed in five of 11 meta-analyses. Glutamine supplementation for critically ill or surgical patients through parenteral or enteral routes appears to reduce the rate of hospital acquired infectious complications and shortening of the length of stay in hospital. Furthermore, glutamine supplementation appeared to reduce the rate of in-patient mortality, but the majority of meta-analyses did not reach statistical significance. However, researchers must appreciate the positive results with caution in light of the fact that there exists statistically significant heterogeneity for the majority of meta-analyses, and statistically significant publication bias in almost half.

Therapeutic Benefits of Glutamine: An Umbrella Review of Meta‐Analyses

IntroductionGlutamine may become a conditionally essential amino acid in patients with catabolic disease as it has been shown that circulating glutamine levels drop during critical illness and following major surgery and this may result in an increase in secondary infection risk, recovery time and mortality rates. However there is much discrepancy in the literature when it comes to randomized controlled studies and so this umbrella review of published meta‐analysis was performed to examine the effectiveness of glutamine's role as a therapeutic agent.MethodsA PubMed, Cochrane Library and CINAHL from January 1st, 1980 to September 30th, 2016 was conducted using the following search strategy: “glutamine AND (meta‐analysis OR systematic review)”. Only English language publications were retrieved which provided quantitative statistical analysis on pooled treatment effects on the relative risks and odds ratios of infectious complications, length of stay in hospital and mortality.ResultsTwenty‐one meta‐analyses were entered into this umbrella review. Fifteen of 19 meta‐analyses found statistically significant reductions of infectious complications with relative risks ranging between 0.42 and 0.93. Twelve of 18 meta‐analyses found statistically significant reductions in the length of stay in hospital with reductions ranging between 0.42 to 4.73 days. Only 4 of 15 meta‐analyses found statistically significant reductions in mortality with relative risks ranging between 0.64 and 1.01. Statistically significant heterogeneity was observed in 16 of 22 meta‐analyses, and publication bias was observed in 5 of 11 meta‐analyses.ConclusionGlutamine supplementation for critically ill or surgical patients through parenteral or enteral routes appears to reduce the rate of hospital acquired infectious complications and shortening of the length of stay in hospital. Glutamine supplementation also appeared to reduce the rate of in‐patient mortality, but the majority of meta‐analyses did not reach statistical significance. However, we must appreciate the positive results with some caution in light of the fact that there exists statistically significant heterogeneity for the majority of meta‐analyses, and statistically significant publication bias in almost half.Support or Funding InformationThere was no funding for this project.

Infection factors of secondary infection in patients with primary immune thrombocytopenia

Objective Explore secondary infection risk factors of patients with primary immune thrombocytopenia (ITP) within 1 year after diagnosed. Methods From July 2007 to July 2015, a total 47 ITP patients with secondary infection within 1 year after diagnosis were included in the study as infection group (n=14), who were chosen from 522 ITP patients in the 100th Hospital of the Chinese People′s Liberation Army. According to the proportion of 1∶1.4, 67 uninfected ITP patients were chosen as non-infection group (n=67) randomly. The clinical features, laboratory findings, treatment methods and curative effects were statistically compared by univariate analysis between two groups, and the clinical indicators which had been resulted by univariate analysis and clinical experiences were included in the multivariate unconditional Logistic regression analysis. The receiver operating characteristic curve(ROC) was taken to analyse the influencing factors on the predictive value of ITP patients with secondary infection. Results ①There were statistically significant differences between two groups in age and complications (t=4.559, χ2=11.400; P<0.001). ②The absolute lymphocyte count (ALC) in infection group was (1.5±0.2)×109/L, which lower than that of non-infection group (1.6±0.1)×109/L, and the levels of C-reactive protein (CRP) and lactate dehydrogenase (LDH) in infection group were (19.6±5.1) mg/L and (286.6±15.7) U/L, respectively , which were higher than those of non-infection group, and the differences were significant (t=-0.369, 2.792, 2.828; P<0.05). ③The number of patients who accepted treatment of splenectomy and rituximab were 7 cases and 4 cases, respectively , which higher than those of non-infection group(1 cases and 0) , and the difference was statistically significant (χ2=7.603, 5.909; P<0.05). ④There was significant difference in clinical effect between two groups (χ2=8.257, P=0.016). ⑤Multivariate Logistic regression analysis showed that age (OR=1.074, 95%CI: 1.025-1.125), LDH (OR=1.021, 95%CI: 1.006-1.035), splenectomy (OR=12.423, 95%CI: 1.252-123.245) were independent risk factors of ITP patients with secondary infection, and ALC (OR=0.051, 95%CI: 0.011-0.243) was independent protective factor of ITP patients with secondary infection. ⑥The best age limit which predicted ITP patients with secondary infection was 47.5 years old, the area under curve(AUC) was 0.718, the sensitivity and specificity were respectively 76.6% and 61.2%; the best ALC value is 0.957×109/L, the AUC was 0.631, the specificity was 85.1%, and the sensitivity was 46.8%; the best LDH value was 183.5 U/L, the AUC was 0.673, the specificity was 35.1%, sensitivity was 92.9%. Conclusions Age, LDH level and splenectomy were independent risk factors of ITP patients with secondary infection with 1 year after diagnosis, ALC was its independent protective factor. All the factors above could better predict the risk of infection. Key words: Thrombocytopenia; Infection; Age of onset; Lymphocyte count; Lactate dehydrogenases

Comparative assessment of primary and secondary infection risks in a norovirus outbreak using a household model simulation

Diarrheal diseases can be transmitted via both primary infection due to exposures to contaminated materials from the environment and secondary infection due to person-to-person contacts. Usually, the importance of secondary infection is empirically assessed by fitting mathematical models to the epidemic curves. However, these empirical models may not be applicable to other epidemic cases because they are developed only for the target epidemics and they don't consider the detail routes of infection. In our previous study, we developed a theoretical model taking into account the various routes of infection that commonly occur in households (e.g., shaking hands, food handling, and changing diapers). This model was made flexible and applicable to any epidemics by means of adjusting model parameters. In this study, we proposed a new index “Vulnerability indicator to secondary infection (VISI)”, which expressed a ratio of secondary infection to primary infection risks and calculated this index in a simulated norovirus (NoV) epidemic that involved 10,000 households. The results demonstrated that households composed of more than three members including infant(s) had much higher levels of VISI (5–45) than two-member-households with VISI (0.1–4). These results concluded that the infants were likely to be a hub of secondary infections in highly dense families and therefore careful handling of diapers was deemed indispensible in such families to effectively control the secondary infections.

Influenza Transmission in a Cohort of Households with Children: 2010-2011

BackgroundHouseholds play a major role in community spread of influenza and are potential targets for mitigation strategies.MethodsWe enrolled and followed 328 households with children during the 2010-2011 influenza season; this season was characterized by circulation of influenza A (H3N2), A (H1N1)pdm09 and type B viruses. Specimens were collected from subjects with acute respiratory illnesses and tested for influenza in real-time reverse transcriptase polymerase chain reaction (RT-PCR) assays. Influenza cases were classified as community-acquired or household-acquired, and transmission parameters estimated.ResultsInfluenza was introduced to 78 (24%) households and transmission to exposed household members was documented in 23 households. Transmission was more likely in younger households (mean age <22 years) and those not reporting home humidification, but was not associated with household vaccination coverage. The secondary infection risk (overall 9.7%) was highest among young children (<9 years) and varied substantially by influenza type/subtype with the highest risk for influenza A (H3N2). The serial interval (overall 3.2 days) also varied by influenza type and was longest for influenza B. Duration of symptomatic illness was shorter in children compared with adults, and did not differ by influenza vaccination status.DiscussionProspective study of households with children over a single influenza season identified differences in household transmission by influenza type/subtype, subject age, and home humidification, suggesting possible targets for interventions to reduce transmission.

Enzymatic activity of a subtilisin homolog, Tk-SP, from Thermococcus kodakarensisin detergents and its ability to degrade the abnormal prion protein

BackgroundTk-SP is a member of subtilisin-like serine proteases from a hyperthermophilic archaeon Thermococcus kodakarensis. It has been known that the hyper-stable protease, Tk-SP, could exhibit enzymatic activity even at high temperature and in the presence of chemical denaturants. In this work, the enzymatic activity of Tk-SP was measured in the presence of detergents and EDTA. In addition, we focused to demonstrate that Tk-SP could degrade the abnormal prion protein (PrPSc), a protease-resistant isoform of normal prion protein (PrPC).ResultsTk-SP was observed to maintain its proteolytic activity with nonionic surfactants and EDTA at 80°C. We optimized the condition in which Tk-SP functions efficiently, and demonstrated that the enzyme is highly stable in the presence of 0.05% (w/v) nonionic surfactants and 0.01% (w/v) EDTA, retaining up to 80% of its activity. Additionally, we also found that Tk-SP can degrade PrPSc to a level undetectable by western-blot analysis.ConclusionsOur results indicate that Tk-SP has a great potential for technological applications, such as thermo-stable detergent additives. In addition, it is also suggested that Tk-SP-containing detergents can be developed to decrease the secondary infection risks of transmissible spongiform encephalopathies (TSE).

Effectiveness of antiviral prophylaxis coupled with contact tracing in reducing the transmission of the influenza A (H1N1-2009): a systematic review

BackgroundDuring the very early stage of the 2009 pandemic, mass chemoprophylaxis was implemented as part of containment measure. The purposes of the present study were to systematically review the retrospective studies that investigated the effectiveness of antiviral prophylaxis during the 2009 pandemic, and to explicitly estimate the effectiveness by employing a mathematical model.MethodsA systematic review identified 17 articles that clearly defined the cases and identified exposed individuals based on contact tracing. Analysing a specific school-driven outbreak, we estimated the effectiveness of antiviral prophylaxis using a renewal equation model. Other parameters, including the reproduction number and the effectiveness of antiviral treatment and school closure, were jointly estimated.ResultsBased on the systematic review, median secondary infection risks (SIRs) among exposed individuals with and without prophylaxis were estimated at 2.1% (quartile: 0, 12.2) and 16.6% (quartile: 8.4, 32.4), respectively. A very high heterogeneity in the SIR was identified with an estimated I2 statistic at 71.8%. From the outbreak data in Madagascar, the effectiveness of mass chemoprophylaxis in reducing secondary transmissions was estimated to range from 92.8% to 95.4% according to different model assumptions and likelihood functions, not varying substantially as compared to other parameters.ConclusionsOnly based on the meta-analysis of retrospective studies with different study designs and exposure settings, it was not feasible to estimate the effectiveness of antiviral prophylaxis in reducing transmission. However, modelling analysis of a single outbreak successfully yielded an estimate of the effectiveness that appeared to be robust to model assumptions. Future studies should fill the data gap that has existed in observational studies and allow mathematical models to be used for the analysis of meta-data.

Transmissibility of Influenza

The authors respond: We thank Farrell and colleagues1 for further discussion on our recent article in Epidemiology.2 In a separate transmission study, we estimated similar secondary infection risks among household contacts of index cases with pandemic and seasonal influenza.3 One concern in that study was whether selecting index cases based on a positive rapid test could have led to bias. The study presently under discussion followed a cohort design, which should minimize such selection bias.2 An advantage of both studies is that pandemic and seasonal influenza viruses were cocirculating, allowing fair comparison between the strains under the same study design and procedures. It is challenging to compare secondary infection risks between different studies, given the substantial effects of study design and procedures.4 Our household study was designed before the 2009 pandemic, and we were able to take the opportunity to estimate the household secondary infection risks. For this reason, we agree with Farrell and colleagues1 that a weakness of our study is the small sample size.5 Rather than aiming to detect small differences in transmissibility, we used the existing data for statistical modeling to qualitatively validate our earlier findings.3 As Farrell and colleagues1 have noted, receipt of influenza vaccination could affect the results. Although valid estimation of secondary infection risks is based on the assumption of uniform susceptibility among household contacts,6 we currently lack good correlates of immunity. In a sensitivity analysis, we excluded everyone who received seasonal vaccine (eAppendix Table 3, https://links.lww.com/EDE/A519) and came to similar conclusions. Including or excluding those with antibody titers ≥1:160 did not change secondary infection risks for seasonal and pandemic strains. In summary, the results on relative transmissibility were not influenced by vaccination and thus we believe are generalizable. We chose to use an age cutoff of 15 years based on early work assessing antibody responses in children and adults7 and because this cutoff was used in several studies addressing transmission of influenza within households.8,9 The immune system undergoes changes during puberty, which would support the use of a threshold at this age or even younger.10 Alternatively, expanding the threshold to include all school-age children would have had minimal effect, as only 16 people (4%) in our study were 15–17 years of age. Finally, we completely agree that there is a critical need to elucidate genetic variation between host generations of influenza infection.11 Brendan Klick School of Public Health The University of Hong Kong Pokfulam Hong Kong Special Administrative Region People's Republic of China Hiroshi Nishiura School of Public Health The University of Hong Kong Pokfulam Hong Kong Special Administrative Region People's Republic of China PRESTO Japan Science and Technology Agency Saitama, Japan Benjamin J. Cowling School of Public Health The University of Hong Kong Pokfulam Hong Kong Special Administrative Region People's Republic of China [email protected]

Household Transmission of 2009 Pandemic Influenza A (H1N1)

During the 2009 influenza A (H1N1) pandemic, household transmission studies were implemented to better understand the characteristics of the transmission of the novel virus in a confined setting. We conducted a systematic review and meta-analysis to assess and summarize the findings of these studies. We identified 27 articles, around half of which reported studies conducted in May and June 2009. In 13 of the 27 studies (48%) that collected respiratory specimens from household contacts, point estimates of the risk of secondary infection ranged from 3% to 38%, with substantial heterogeneity. Meta-regression analyses revealed that a part of the heterogeneity reflected varying case ascertainment and study designs. The estimates of symptomatic secondary infection risk, based on 20 studies identifying febrile acute respiratory illness among household contacts, also showed substantial variability, with point estimates ranging from 4% to 37%. Transmission of the 2009 pandemic virus in households appeared to vary among countries and settings, with differences in estimates of the secondary infection risk also partly due to differences in study designs.

Secondary heterologous dengue infection risk: Disequilibrium between immune regulation and inflammation?

Increased serum levels of cytokines released by cells of the immune response have been detected in patients suffering from dengue disease. Likewise, secondary infections by a different dengue virus serotype result in a highest risk of development of the severe dengue disease. Both findings suggest that the memory immune response is one of the key players in the pathogenesis of this disease. Here we take advantage of the particular Cuban epidemiological situation in dengue to analyze a broad spectrum of cell-mediated immune response mediators at mRNA and protein level. Evidences for a regulatory immune pattern in homologous (TGF-β, IL-10) vs. pro-inflammatory pattern (IFN-γ, TNF-α) in heterologous dengue virus re-challenge were found, suggesting a possible association with the higher incidence of severe dengue cases in the latter case.

Monocytic HLA-DR expression in intensive care patients: Interest for prognosis and secondary infection prediction*

To test early measurement of human leukocyte antigen-DR expression on circulating monocytes (mHLA-DR) as prognostic marker, and the trend of mHLA-DR recovery for the prediction of late secondary infection risk in a large intensive care unit population. Prospective, observational study over 16 mos. Intensive care unit in a tertiary teaching hospital. Simplified Acute Physiology Score II >15, age >18 yrs. The mHLA-DR was measured by flow cytometry within the first 3 days and twice a week until discharge. We used a logistic regression model for outcome prediction, and a competing risk approach to test the relationship between mHLA-DR recovery (log (mHLA-DR) slope) and incidence of secondary infection. A total of 283 consecutive patients suffering from various pathologies were monitored (Simplified Acute Physiology Score II = 39, Sepsis-related Organ Failure Assessment of 5 on day 0). Early mHLA-DR was decreased in the whole population, however, more deeply in sepsis (p < .0001). Low mHLA-DR was associated with mortality in the whole population (p = .003), as in subgroups (nonseptic, neurologic, and septic), but not when adjusted on Simplified Acute Physiology Score II. In patients with a length of stay of >7 days (n = 70), the lower the slope of mHLA-DR recovery, the higher the incidence of the first secondary infection (adjusted on early mHLA-DR, p = .04). For a given severity, mHLA-DR proved not to a predictive marker of outcome, but a weak trend of mHLA-DR recovery was associated with an increased risk of secondary infection. Monitoring immune functions through mHLA-DR in intensive care unit patients therefore could be useful to identify a high risk of secondary infection.