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James W. Rudge, Nui Inthalaphone, Rebecca Pavlicek, Phimpha Paboriboune, Bruno Flaissier, Chou Monidarin, Nicolas Steenkeste, Viengmon Davong, Manivanh Vongsouvath, K. A. Bonath, Melinda Messaoudi, Mitra Saadatian-Elahi, Paul Newton, Hubert Endtz, David Dance, Glaucia Paranhos Baccala, Valentina Sanchez Picot
by James W. Rudge, Nui Inthalaphone, Rebecca Pavlicek, Phimpha Paboriboune, Bruno Flaissier, Chou Monidarin, Nicolas Steenkeste, Viengmon Davong, Manivanh Vongsouvath, K. A. Bonath, Melinda Messaoudi, Mitra Saadatian-Elahi, Paul Newton, Hubert Endtz, David Dance, Glaucia Paranhos Baccala, Valentina Sanchez Picot
Respiratory diseases are a major contributor to morbidity and mortality in many tropical countries, including Lao PDR. However, little has been published regarding viral or bacterial pathogens that can contribute to influenza-like illness (ILI) in a community setting. We report on the results of a community-based surveillance that prospectively monitored the incidence of ILI and its causative pathogens in Vientiane capital in Lao PDR. A cohort of 995 households, including 4885 study participants, were followed-up between May 2015 and May 2016. Nasopharyngeal swabs, throat swabs, and sputum specimens were collected from ILI cases identified through active case-finding. Real-Time PCR was used to test nasopharyngeal swabs for 21 respiratory pathogens, while throat and sputum samples were subjected to bacterial culture. Generalized linear mixed models were used to assess potential risk factors for associations with ILI. In total, 548 episodes of ILI were reported among 476 (9.7%) of the study participants and 330 (33.2%) of the study households. The adjusted estimated incidence of ILI within the study area was 10.7 (95%CI: 9.4–11.9) episodes per 100 person-years. ILI was significantly associated with age group (p
Anne-Flore Plane, Pierre-Emmanuel Marsan, Damien du Cheyron, Xavier Valette
A 58-year-old man was hospitalised in our intensive care unit for severe, acute respiratory distress syndrome caused by an influenza virus infection. After 31 days, he was gradually weaned off mechanical ventilation. However, on the day after extubation, he had to be reintubated because of further respiratory distress. Emergency intubation was performed after rapid sequence induction using the short-acting anaesthetic agent etomidate, intravenously, at a dose of 0·3 mg/kg, and the muscle relaxant succinylcholine, intravenously, at a dose of 1 mg/kg.
Geraint B Rogers
Acute lower respiratory tract infections (LRTIs) are a major source of early life morbidity and the principal infectious cause of infant mortality.1 A growing body of research suggests that the microbiome of the upper respiratory tract substantially influences the incidence and severity of LRTIs. The nasopharyngeal mucosa is the first line of defence against airborne pathogens. In addition to the mechanisms of host innate immunity, the commensal microbiota suppresses the expansion of populations of opportunistic pathogens that are common in the nasopharynx—including Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus—through a combination of competitive exclusion, suppression of virulence through direct inter-species interaction, and regulation of local immunity.
Lindsey BB, Armitage EP, Kampmann B, de Silva TI. The efficacy, effectiveness, and immunogenicity of influenza vaccines in Africa: a systematic review. Lancet Infect Dis 2019; 19: e110–19—Figure 2 and the panel have been corrected. These corrections have been made to the online version as of April 16, 2019.
Colin R Simpson, Dan Beever, Kirsty Challen, Daniela De Angelis, Ellen Fragaszy, Steve Goodacre, Andrew Hayward, Wei Shen Lim, G James Rubin, Malcolm G Semple, Marian Knight, NIHR hibernated influenza studies collaborative group
The 2009 influenza A H1N1 pandemic was responsible for considerable global morbidity and mortality. In 2009, several research studies in the UK were rapidly funded and activated for clinical and public health actions. However, some studies were too late for their results to have an early and substantial effect on clinical care, because of the time required to call for research proposals, assess, fund, and set up the projects. In recognition of these inherent delays, a portfolio of projects was funded by the National Institute for Health Research in 2012.
Catherine Cordonnier, Sigrun Einarsdottir, Simone Cesaro, Roberta Di Blasi, Malgorzata Mikulska, Christina Rieger, Hugues de Lavallade, Giuseppe Gallo, Thomas Lehrnbecher, Dan Engelhard, Per Ljungman, European Conference on Infections in Leukaemia group
Infection is a main concern after haemopoietic stem cell transplantation (HSCT) and a major cause of transplant-related mortality. Some of these infections are preventable by vaccination. Most HSCT recipients lose their immunity to various pathogens as soon as the first months after transplant, irrespective of the pre-transplant donor or recipient vaccinations. Vaccination with inactivated vaccines is safe after transplantation and is an effective way to reinstate protection from various pathogens (eg, influenza virus and Streptococcus pneumoniae), especially for pathogens whose risk of infection is increased by the transplant procedure.
Julien Coussement, David Lebeaux, Najla El Bizri, Vincent Claes, Michel Kohnen, Deborah Steensels, Isabelle Étienne, Hélène Salord, Emmanuelle Bergeron, Veronica Rodriguez-Nava
by Julien Coussement, David Lebeaux, Najla El Bizri, Vincent Claes, Michel Kohnen, Deborah Steensels, Isabelle Étienne, Hélène Salord, Emmanuelle Bergeron, Veronica Rodriguez-Nava
Background Transplant recipients are at risk of pulmonary nocardiosis, a life-threatening opportunistic infection caused by Nocardia species. Given the limitations of conventional diagnostic techniques (i.e., microscopy and culture), a polymerase chain reaction (PCR)-based assay was developed to detect Nocardia spp. on clinical samples. While this test is increasingly being used by transplant physicians, its performance characteristics are not well documented. We evaluated the performance characteristics of this test on bronchoalveolar lavage (BAL) fluid samples from lung transplant recipients (LTRs). Methods We prospectively included all BAL samples from LTRs undergoing bronchoscopy at our institution between December 2016 and June 2017 (either surveillance or clinically-indicated bronchoscopies). Presence of microbial pathogens was assessed using techniques available locally (including microscopy and 10-day culture for Nocardia). BAL samples were also sent to the French Nocardiosis Observatory (Lyon, France) for the Nocardia PCR-based assay. Transplant physicians and patients were blinded to the Nocardia PCR results. Results We included 29 BAL samples from 21 patients (18 surveillance and 11 clinically-indicated bronchoscopies). Nocardiosis was not diagnosed in any of these patients by conventional techniques. However, Nocardia PCR was positive in five BAL samples from five of the patients (24%, 95% confidence interval: 11–45%); four were asymptomatic and undergoing surveillance bronchoscopy, and one was symptomatic and was later diagnosed with influenza virus infection. None of the five PCR-positive patients died or were diagnosed with nocardiosis during the median follow-up of 21 months after the index bronchoscopy (range: 20–23 months). Conclusions In this prospective study, Nocardia PCR was positive on BAL fluid from one fourth of the LTRs. Nocardia PCR-based assays should be used with caution on respiratory samples from LTRs because of the possible detection of airway colonization using this technique. Larger studies are required to determine the usefulness of the Nocardia PCR-based assay in transplant recipients.
Tatiana Schäffer Gregianini,
Claudete Farina Seadi,
Luiz Domingos Zavarize Neto,
Letícia Garay Martins,
Guilherme Cerutti Muller,
Selir Maria Straliotto,
Ana Beatriz Gorini da Veiga
Human parainfluenza virus (hPIV) is an important pathogen in respiratory infections, however the health burden of hPIV is underestimated. This study describes the infections by hPIV1‐3 in Rio Grande do Sul, Brazil, from 1990 to 2017, providing data of the frequency and seasonality of cases and associated clinical symptoms.
Method of study
Nasopharyngeal samples of patients with respiratory infection were collected, clinical data were analyzed, and immunofluorescence was used to detect hPIV.
Respiratory viruses were detected in 33.63% of respiratory infections. In a total of 11 606 cases of viral respiratory infection, 781 were positive for hPIV; hPIV prevalence ranged from 2.14% to 27% of viral respiratory infections. hPIV1 circulates mainly during fall; hPIV3 circulation, in turn, starts in fall and peaks during spring; and cases of hPIV2 are reported along the year, with peaks in fall and early spring. The most affected age group was children, with hPIV prevalence of 74.23% in patients for less than 1 year. A higher proportion of girls were infected than boys, however, no difference by sex was observed considering all age groups. The most frequent type was hPIV3, especially in hospitalized patients. Both hPIV1 and 3 were associated with dyspnea, while hPIV2 caused mild symptoms mainly in nonhospitalized patients. Nineteen fatalities occurred, 89.5% of them associated with risk factors (prematurity; chronic diseases; age, 60 years).
hPIV causes a high number of respiratory infections, leading to hospitalization especially in children; epidemiological and surveillance studies are important for the control and management of respiratory infections.
Rowe, H. M., Mann, B., Iverson, A., Poole, A., Tuomanen, E., Rosch, J. W.
Acute otitis media is one of the most common childhood infections worldwide. Currently licensed vaccines against the common otopathogen, Streptococcus pneumoniae, target the bacterial capsular polysaccharide and confer no protection against non-encapsulated strains or capsular types outside of vaccine coverage. Mucosal infections such as acute otitis media remain prevalent, even those caused by vaccine-covered serotypes. Here we report that a protein-based vaccine, a fusion construct of epitopes of CbpA to pneumolysin toxoid, confers effective protection against pneumococcal acute otitis media for non-PCV-13 serotypes and enhances protection for PCV-13 serotypes when co-administered with PCV-13. Having crossreactive epitopes, the fusion protein also induces potent antibody responses against non-typeable Haemophilus influenzae and S. pneumoniae, engendering protection against acute otitis media caused by emerging unencapsulated otopathogens. These data suggest that augmenting capsule-based vaccination with conserved, cross-reactive protein-based vaccines may broaden and enhance protection against acute otitis media.
Karawita, Anjana C.; Tong, Marcus Z.W.; Short, Kirsty R.
Purpose of review
A delicate balance exists between a protective and detrimental immune response to an invading viral pathogen. Here, we review the latest advancements in our understanding of immunity and immunopathology during H7N9 influenza A virus (IAV) infections and its relevance to disease management and diagnosis.
Recent studies have highlighted the role of specific leukocytes in the pathogenesis of H7N9 IAV infections and potential diagnostic role that host cytokine profiles can play in forecasting disease severity. Furthermore, alterations in diet have emerged as a possible preventive measure for severe IAV infections.
The recent emergence and continued evolution of H7N9 IAVs have emphasized the threat that these avian viruses pose to human health. Understanding the role of the host immune response in both disease protection and pathogenesis is an essential first step in the creation of novel therapeutic and preventive measures for H7N9 IAV infections.
Correspondence to Kirsty R. Short, Brisbane, Qld Australia. Tel: +61 7 3365 3732; e-mail: email@example.com
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
Han A, Czajkowski L, Donaldson A, et al.
AbstractBackgroundThe development of vaccines and therapeutics have relied on healthy volunteer influenza challenge studies. A validated human infection model with wild-type A(H1N1)pdm09 was reported previously.ObjectiveTo characterize a wild-type Influenza A/Bethesda/MM1/H3N2 challenge virus in healthy volunteers.MethodsParticipants received a single dose of a cell-based, reverse-genetics, GMP-produced wild-type influenza A/H3N2/2011 virus intranasally and were isolated at the NIH Clinical Center for > 9 days. Dose escalation was performed from 104 to 107 TCID50. Viral shedding and clinical disease were evaluated daily.ResultsOf 37 participants challenged, 16 (43%) had viral shedding and 27 (73%) developed symptoms with 12 participants (32%) experiencing mild to moderate influenza disease (MMID) defined as shedding and symptoms. Only participants receiving the 106 and 107 TCID50 doses experienced MMID at 44% and 40%, respectively. Symptom severity peaked on day 3 while most viral shedding occurred 1-2 days after challenge. Only 10 (29%) participants had > fourfold rise in hemagglutinin inhibition (HAI) antibody titer after challenge.ConclusionsThe A/Bethesda/MM1/H3N2 challenge virus safely induced MMID in healthy volunteers, but caused less MMID than the A(H1N1)pdm09 challenge virus even at the highest dose. There was less detection of shedding though the incidence of symptoms was similar to A(H1N1)pdm09. Fewer serum anti-HA antibody responses with less MMID indicate that preexisting immunity factors other than anti-HA antibody may limit shedding in healthy volunteers. This A/Bethesda/MM1/H3N2 challenge virus can be utilized in future studies to further explore pathogenesis and immunity and to evaluate vaccine candidates.
In this work, we report a fluorescence method for homogeneous detection of influenza A (H1N1) DNA sequence based on G‐quadruplex‐NMM complex and Assistance DNA (A‐DNA) inhibition. The quadruplex‐based functional DNA (QBF‐DNA), composed of complementary probe to the target H1N1 DNA sequence and G‐rich fragment, was designed as the signal DNA. The A‐DNA consisted of two parts, one part was complementary to target H1N1 DNA and the other part was complementary to the signal DNA. In the absence of target H1N1 DNA, the G‐rich fragment of QBF‐DNA can form G‐quadruplex‐NMM complex, which outputted a fluorescent signal. With the presence of target H1N1 DNA, QBF‐DNA and A‐DNA can simultaneously hybridize with target H1N1 DNA to form double‐helix structure. In this case, the A‐DNA partially hybridized with the QBF‐DNA, which inhibited the formation of G‐quadruplex‐NMM complex, leading to the decrease of fluorescent signal. Under the optimum conditions, the fluorescence intensity was inversely proportional to the concentration of target H1N1 DNA over the range from 25pmol/L to 700pmol/L with a detection limit of 8pmol/L. In addition, the method is target specific and practicability, and would become a new diagnostic assay for influenza A (H1N1) DNA sequence and other infectious diseases.
This article is protected by copyright. All rights reserved.
Detecting the onset of influenza epidemic is important for epidemiological surveillance and for investigating the factors driving spatiotemporal transmission patterns. Most approaches define the epidemic onset based on thresholds, which use subjective criteria and are specific to individual surveillance systems.
We applied the empirical threshold method (ETM), together with two non-thresholding methods, including the maximum curvature method (MCM) that we proposed and the segmented regression method (SRM), to determine onsets of influenza epidemics in each prefecture of Japan, using sentinel surveillance data of influenza-like illness (ILI) from 2012/2013 through 2017/2018. Performance of the MCM and SRM was evaluated, in terms of epidemic onset, end, and duration, with those derived from the ETM using the nationwide epidemic onset indicator of 1.0 ILI case per sentinel per week.
The MCM and SRM yielded complete estimates for each of Japan’s 47 prefectures. In contrast, ETM estimates for Kagoshima during 2012/2013 and for Okinawa during all six influenza seasons, except 2013/2014, were invalid. The MCM showed better agreement in all estimates with the ETM than the SRM (R2 = 0.82, p
Jia W, Wen X, Xie S, et al.
To the Editor—In their recent article, Ning et al  analyzed antigenic drift of influenza A(H7N9) virus haemagglutinin (HA). Their findings showed that some key mutations affecting antigenicity may have appeared in H7N9 in the past 5 years. To further evaluate the changes of antigenicity of H7N9, we studied the antigenicity and molecular characteristics of a new H7N9 virus isolated from poultry. We found a novel antigenic drift, which is different from previous findings. To our knowledge, this is the first antigenic change found after the implementation of China’s immunization policy in poultry.
Jianjian Wei, Jie Zhou, Yakun Liu, Jie Wu, Tao Jin, Yuguo Li, Hui-Ling Yen
by Jianjian Wei, Jie Zhou, Yakun Liu, Jie Wu, Tao Jin, Yuguo Li, Hui-Ling Yen
Infectious virus-laden aerosols generated during poultry processing may mediate airborne transmissions of avian influenza at live poultry markets. To develop effective control measures to reduce aerosol dispersion, we characterised the aerosol flow pattern of the mechanical defeatherers, a major source of aerosol dispersion during poultry processing at live poultry markets in China. Mechanical defeatherers create a strong air circulation during operation with inflow and outflow velocities over 1 m/s. A partial lid was designed to suppress the outflow and reduce aerosol dispersion. Computational fluid dynamics simulations confirmed that the partial lid prototype reduced the aerosol escape rate by over 65%. To validate the effectiveness of the partial lid in reducing aerosol dispersion, a field study was conducted at a retail poultry shop in Guangzhou and the concentrations of influenza viral RNA and avian 18S rRNA dispersed in air were monitored during poultry processing, with and without the use of the partial lid. At the breathing zone of the poultry worker, the use of the partial lid effectively suppressed the upward airflow and reduced the concentration of avian 18S rRNA in the air by 57%. The economic and practical partial lid can be easily implemented to reduce generation of influenza virus-laden aerosols at live poultry markets.
Breanna Hodgins, Stephane Pillet, Nathalie Landry, Brian James Ward
by Breanna Hodgins, Stephane Pillet, Nathalie Landry, Brian James Ward
Background The elderly are at high risk from influenza, in part because immunity wanes with age and through the accumulation of comorbidities. A novel plant-derived virus-like-particle (VLP) vaccine bearing influenza hemagglutinin can induce a balanced humoral and cellular response in old mice (16–18 months) while split virion vaccines elicit mostly antibodies. Because mice also collect comorbidities and lose immune competence as they age, we wished to determine how the plant-derived VLP vaccine would perform in animals approaching the end of their life-span. Materials and methods Old (24–26 months) female BALB/c mice received two intramuscular doses of H1-VLP vaccine, an inactivated H1N1 vaccine (IIV) (both based on A/H1N1/California/07/09) (3μg each) or PBS. Serum was collected on day 42 and humoral responses were measured by enzyme-linked immunosorbent assay (ELISA), microneutralization (MN) and hemagglutination inhibition (HI) assays. Influenza-specific splenocyte CD4+ & CD8+ T cell responses were measured by flow cytometry. Full body computed tomography (CT) and structured necropsies were performed on day 42. Comorbidities including reduced lung volume (kyphosis), masses, abscesses, etc. were assessed using a standard scoring system (1–21) and mice with scores ≥5 were considered to have important comorbidities. Results Overall, 53.3% of the animals had significant comorbidities. Three weeks post-boost, HI and MN titres were mostly undetectable but ELISA titres were significantly higher in the H1-VLP animals compared to the IIV group (GMT (95% CI): 961 (427, 2163) vs 425 (200, 903): p = 0.03). Both CD4+(TNFα, IFNγ) and CD8+ (IFNγ) T cell responses were also greater in the H1-VLP group than the IIV. Conclusions Even in very old mice with comorbidities, the plant-made H1-VLP vaccine elicited a stronger and more balanced immune response than IIV. Animals with fewer comorbidities tended to have the better composite (humoral and cellular) responses. These novel vaccines have the potential to address some of the limitations of current vaccines in the elderly.
Ysebaert, C., Denoël, P., Weynants, V., Bakaletz, L. O., Novotny, L. A., Godfroid, F., Hermand, P.
PE-PilA is a fusion protein composed of immunologically relevant parts of protein E (PE) and the majority subunit of the type IV pilus (PilA), two major antigens of nontypeable Haemophilus influenzae (NTHi). Here we report on the preclinical evaluation of PE-PilA as vaccine antigen. The immunogenic potential of PE and PilA within the fusion was compared with that of isolated PE and PilA antigens.When injected intramuscularly in mice, the immunogenicity of PE within the fusion was equivalent to that of isolated PE, except when formulated with alum. In contrast, in our murine models PilA was consistently found more immunogenic as a sub-entity of the PE-PilA fusion protein than when injected as an isolated antigen. Anti-PE antibodies following immunization with PE-PilA, demonstrated the same capacity to inhibit the binding of PE to vitronectin than those induced after PE immunization. Likewise, PE-PilA-induced anti-PilA antibodies inhibited the formation of NTHi biofilms and disrupted established biofilms in vitro. These experiments support the immunogenic equivalence between fused PE-PilA and isolated PE and PilA, respectively. Further, the potential of PE-PilA immunization against NTHi-induced disease was evaluated. After intranasal NTHi challenge, colonisation of the murine nasopharynx significantly dropped in animals formerly immunized with PE-PilA, and in chinchillas, signs of otitis media were significantly reduced in animals that have received anti-PE-PilA antibodies.Taken together, our data support the use of PE-PilA as an NTHi vaccine antigen.
Avian influenza A (H5N6) virus poses a great threat to the human health since it is capable to cross the species barrier and infect humans. Although human infections are believed to largely originate from poultry contaminations, the transmissibility is unclear and only limited information was available on poultry environment contaminations, especially in Fujian Province.
A total of 4901 environmental samples were collected and tested for Avian Influenza Virus (AIV) from six cities in Fujian Province through the Fujian Influenza Surveillance System from 2013 to 2017. Two patient-related samples were taken from Fujian’s first confirmed H5N6 human case and his backyard chicken feces in 2017. Chi-square test or Fisher’s exact probability test was used to compare the AIV and the viral subtype positive rates among samples from different Surveillance cities, surveillance sites, sample types, and seasons. Phylogenetic tree analysis and molecular analysis were conducted to track the viral transmission route of the human infection and to map out the evolutions of H5N6 in Fujian.
The overall positive rate of the H5 subtype AIVs was 4.24% (208/4903). There were distinctive differences (p
Najat Bdeir, Prerna Arora, Sabine Gärtner, Markus Hoffmann, Udo Reichl, Stefan Pöhlmann, Michael Winkler
by Najat Bdeir, Prerna Arora, Sabine Gärtner, Markus Hoffmann, Udo Reichl, Stefan Pöhlmann, Michael Winkler
Influenza A virus (IAV) infection poses a serious health threat and novel antiviral strategies are needed. Defective interfering particles (DIPs) can be generated in IAV infected cells due to errors of the viral polymerase and may suppress spread of wild type (wt) virus. The antiviral activity of DIPs is exerted by a DI genomic RNA segment that usually contains a large deletion and suppresses amplification of wt segments, potentially by competing for cellular and viral resources. DI-244 is a naturally occurring prototypic segment 1-derived DI RNA in which most of the PB2 open reading frame has been deleted and which is currently developed for antiviral therapy. At present, coinfection with wt virus is required for production of DI-244 particles which raises concerns regarding biosafety and may complicate interpretation of research results. Here, we show that cocultures of 293T and MDCK cell lines stably expressing codon optimized PB2 allow production of DI-244 particles solely from plasmids and in the absence of helper virus. Moreover, we demonstrate that infectivity of these particles can be quantified using MDCK-PB2 cells. Finally, we report that the DI-244 particles produced in this novel system exert potent antiviral activity against H1N1 and H3N2 IAV but not against the unrelated vesicular stomatitis virus. This is the first report of DIP production in the absence of infectious IAV and may spur efforts to develop DIPs for antiviral therapy.
In the spring of 1918, the “War to End All Wars”, which would ultimately claim more than 37 million lives, had entered into its final year and would change the global political and economic landscape forever. At the same time, a new global threat was emerging and would become one of the most devastating global health crises in recorded history.
The 1918 H1N1 pandemic virus spread across Europe, North America, and Asia over a 12-month period resulting in an estimated 500 million infections and 50–100 million deaths worldwide, of which ~ 50% of these occurred within the fall of 1918 (Emerg Infect Dis 12:15-22, 2006, Bull Hist Med 76:105-115, 2002). However, the molecular factors that contributed to the emergence of, and subsequent public health catastrophe associated with, the 1918 pandemic virus remained largely unknown until 2005, when the characterization of the reconstructed pandemic virus was announced heralding a new era of advanced molecular investigations (Science 310:77-80, 2005). In the century following the emergence of the 1918 pandemic virus we have landed on the Moon, developed the electronic computer (and a global internet), and have eradicated smallpox. In contrast, we have a largely remedial knowledge and understanding of one of the greatest scourges in recorded history.
Here, we reflect on the 1918 influenza pandemic, including its emergence and subsequent rapid global spread. In addition, we discuss the pathophysiology associated with the 1918 virus and its predilection for the young and healthy, the rise of influenza therapeutic research following the pandemic, and, finally, our level of preparedness for future pandemics.
Sarah F. Andrews, Michael J. Chambers, Chaim A. Schramm, Jason Plyler, Julie E. Raab, Masaru Kanekiyo, Rebecca A. Gillespie, Amy Ransier, Sam Darko, Jianfei Hu, Xuejun Chen, Hadi M. Yassine, Jeffrey C. Boyington, Michelle C. Crank, Grace L. Chen, Emily Coates, John R. Mascola, Daniel C. Douek, Barney S. Graham, Julie E. Ledgerwood, Adrian B. McDermott
Influenza vaccination occurs in the context of pre-existing immunity. Andrews et al. compare the pre-existing memory IgG B cell response recognizing conserved epitopes on influenza hemagglutinin with the newly generated response to strain-specific epitopes upon H7N9 vaccination. The differences in magnitude, phenotype, and affinity maturation between the two responses highlight the challenges in achieving long-lasting, broad protection against an ever-evolving virus.
We studied the incidence, morbidity and mortality of all patients presenting in our teaching hospital with proven influenza virus and/or respiratory syncytial virus (RSV) infection during the influenza epidemic season 2018 which was characterized by a predominant incidence of influenza virus B type B of the Yamagata line.
In the fall of 2017, specific precaution measures in addition to standard measures were implemented, including standardized testing for influenza virus A,B and RSV by multiplex PCR of pharyngeal swabsData from all consecutive patients were analyzed retrospectively.
Overall 651 patients were examined for the presence of influenza virus and RSV; 214 patients had influenza virus A (n = 36), B (n = 152), and/or RSV (n = 30), including four patients with dual infection. 86% of cases had influenza virus (80% B), and 14% RSV infection. N = 23 cases were treated as outpatients. The rate of acute viral respiratory infections (influenza virus and RSV) was 191 of 2776 (6.9%) admissions to medical wards. Of n = 191 hospitalized cases, n = 44 cases (20.6%) had nosocomial infection. Viral infections were associated with a high morbidity (pneumonia 28.5%, mortality 4.7%). Independent predictors of prolonged hospitalization were the presence of pneumonia, NIV and renal complications, and independent predictors of pneumonia were age ≥ 65 years, bedridden status and CRP ≥ 2.9 mg/dL.
The rate of nosocomial cases was high despite established precaution measures. RSV was associated with morbidity and mortality comparable to influenza. Pneumonia remains the main complication of acute viral respiratory infections, and antimicrobial treatment should include both antiviral as well as antibacterial agents.
Phillips, Z. N., Brizuela, C., Jennison, A. V., Staples, M., Grimwood, K., Seib, K. L., Jennings, M. P., Atack, J. M.
Non-typeable Haemophilus influenzae (NTHi) is a major human pathogen, responsible for several acute and chronic infections of the respiratory tract. The incidence of invasive infections caused by NTHi is increasing world-wide. NTHi is able to colonise the nasopharynx asymptomatically, and the exact change(s) responsible for transition from benign carriage to overt disease are not understood. We have previously reported that phase-variation (the rapid and reversible ON-OFF switching of gene expression) of particular lipooligosaccharide (LOS) glycosyltransferases occurs during transition from colonising the nasopharynx to invading the middle ear. Variation in the structure of the LOS is dependent on the ON/OFF expression status of each of the glycosyltransferases responsible for LOS biosynthesis. In this study we surveyed a collection of invasive NTHi isolates for ON/OFF expression status of seven phase-variable LOS glycosyltransferases. We report that the expression state of the LOS biosynthetic genes oafA ON and lic2A OFF show a correlation with invasive NTHi isolates. We hypothesise that these gene expression changes contribute to the invasive potential of NTHi. OafA expression, which is responsible for the addition of an O-acetyl group onto the LOS, has been shown to impart a phenotype of increased serum resistance, and may serve as a marker for invasive NTHi.
Laura K. Borkenhagen, Mo D. Salman, Mai-Juan Ma, Gregory C. Gray
Paukner, S., Gelone, S. P., Arends, S. J. R., Flamm, R. K., Sader, H. S.
Lefamulin, the first semisynthetic pleuromutilin antibacterial for intravenous and oral treatment of community-acquired bacterial pneumonia (CABP), and comparators were evaluated for in vitro activity against a global collection of pathogens commonly causing CABP (n=8595) from the 2015–2016 SENTRY Antimicrobial Surveillance Program. Lefamulin was highly active against pathogens commonly Streptococcus pneumoniae including multidrug resistant and extensively drug resistant strains (MIC50/90 for total and resistant subsets, 0.06/0.12 μg/mL; 100% inhibited at ≤1 μg/mL), Staphylococcus aureus including MRSA (both MIC50/90, 0.06/0.12 μg/mL; 99.8% and 99.6% inhibited at ≤1 μg/mL, respectively), Haemophilus influenzae (MIC50/90, 0.5/1 μg/mL; 93.8% inhibited at ≤1 μg/mL), and Moraxella catarrhalis (MIC50/90, 0.06/0.12 μg/mL; 100% inhibited at ≤0.25 μg/mL), and its activity was unaffected by resistance to other antibacterial classes.
Levine M, Martin E, Petrie J, et al.
AbstractBackgroundInfluenza vaccine effectiveness was low in 2017-2018, yet circulating A(H3N2) viruses were antigenically similar to cell-grown vaccine strains. Notably, most influenza vaccines are egg-propagated.MethodsSerum was collected shortly after illness onset from 15 A(H3N2) infected cases and 15 uninfected hospitalized adults. Geometric mean titers against egg- and cell-grown A/Hong Kong/4801/2014 A(H3N2) vaccine strains and representative circulating viruses (including A/Washington/16/2017) were determined by microneutralization (MN). Independent effects of strain-specific titers on susceptibility were estimated by logistic regression.ResultsMN titers against egg-A/Hong Kong were significantly higher among vaccinated individuals (173 vs 41; p=0.01). In unadjusted models, a 2-fold increase in titers against egg-A/Hong Kong was not significantly protective (29% reduction; p=0.09), but a similar increase in cell-A/Washington titer (3C.2a2) was protective (60% reduction; p=0.02). Higher egg-A/Hong Kong titers were not significantly associated with infection, when adjusted for titers against A/Washington (15% reduction; p=0.61). A 54% reduction of odds of infection was observed with a 2-fold increase in A/Washington (not significant), adjusted for egg-A/Hong Kong titer.ConclusionIndividuals vaccinated in 2017-2018 had high antibody titers against the egg-adapted vaccine strain and lower titers against circulating viruses. Titers against circulating, but not egg-adapted strains, were correlated with protection.
Crowe J, Jr.
AbstractUnderstanding the antigenic variation in circulating influenza virus strains and how the human immune system recognizes diverse virus strains is one of the central challenges of our time for human vaccinologists. Antibodies directed to the two major integral membrane proteins on the surface of viral particles, hemagglutinin (HA) and neuraminidase (NA), mediate protection against reinfection following natural infection or vaccination, but the HA and NA proteins in field strains are highly variable in sequence. The central questions about influenza immunity today are how to achieve protective antibody responses in a higher proportion of individuals, and how to induce responses with more breadth and more durability. Recent studies using isolation of human monoclonal antibodies followed by structural and functional characterization have revealed conserved antigenic sites that are recognized by broadly cross-reactive antibodies. The antigenic landscape on the HA and NA proteins is coming into focus in a way that informs new studies of the correlates and mechanisms of immunity. Understanding the antibody determinants of influenza immunity points the way toward development and testing of next generation vaccines that have the potential to confer broadly protective immunity.
R. Bai et al.
Hadara L. Norowitz, Timothy Morello, Hadassah M. Kupfer, Stephan A. Kohlhoff, Tamar A. Smith-Norowitz
by Hadara L. Norowitz, Timothy Morello, Hadassah M. Kupfer, Stephan A. Kohlhoff, Tamar A. Smith-Norowitz
This study aims to assess prospectively whether there is an association between frequencies of upper respiratory tract infections (URTI) or asthma in early childhood and failed otoacoustic emission (OAE) screenings later in life. There are no clear recommendations for hearing testing following acute otitis media (AOM) infection. This is a retrospective, practice based chart review. Participants from a primary care setting were 517 pre-adolescent and adolescent children (49.9% female) (ages 10–21; mean, 15 y/o), who had presented with at least one specific bacterial URTI (AOM, Group A Streptococcus (GAS) tonsillitis, or Influenza) during childhood. Hearing testing was recorded incidentally at all subsequent routine health care maintenance visits (OAE hearing screen). Simple linear regression analyses were performed using R (v3.4.4). We found that number of episodes of AOM infections strongly correlated with number of failed OAE screenings later in life (F = 76.37; P =
Ching-Fu Weng, Li-Ju Chen, Chih-Wan Lin, Ho-Min Chen, Henry Hsin-Chung Lee, Thai-Yen Ling, Fei-Yuan Hsiao
Redlberger-Fritz M, Vietzen H, Puchhammer-Stöckl E.
AbstractNK-cell response against influenza viruses partly depends on expression of CD112, a ligand for NK-cell receptor CD226 (DNAM-1). We analyzed whether distinct CD226 variants are associated with influenza disease severity. Comparison between 145 patients hospitalized with severe influenza at intensive care units (ICU) with 139 matched influenza-positive outpatients showed that especially presence of the rs763362 G allele (GG, AG) was associated with occurrence of severe influenza infections (p=0.0076). Also a higher frequency of the rs727088 G allele and rs763361 T allele were observed in the ICU group. Thus, CD226 variants may contribute to the severity of influenza virus disease.
Corinne Levy, Emmanuelle Varon, Naim Ouldali, Alain Wollner, Franck Thollot, François Corrard, Andreas Werner, Stéphane Béchet, Stéphane Bonacorsi, Robert Cohen
by Corinne Levy, Emmanuelle Varon, Naim Ouldali, Alain Wollner, Franck Thollot, François Corrard, Andreas Werner, Stéphane Béchet, Stéphane Bonacorsi, Robert Cohen
After pneumococcal conjugate vaccine (PCV) implementation, the number of acute otitis media (AOM) episodes has decreased, but AOM still remains among the most common diagnoses in childhood. From 2% to 17% of cases of AOM feature spontaneous perforation of the tympanic membrane (SPTM). The aim of this study was to describe the bacteriological causes of SPTM 5 to 8 years years after PCV13 implementation, in 2010. From 2015 to 2018, children with SPTM were prospectively enrolled by 41 pediatricians. Middle ear fluid was obtained by sampling spontaneous discharge. Among the 470 children with SPTM (median age 20.8 months), no otopathogen was isolated for 251 (53.4% [95% CI 48.8%;58.0%]): 47.1% of infants and toddlers, 68.3% older children (p
Due to the importance of Chronic obstructive pulmonary disease (COPD) as the fourth cause of mortality worldwide and the lack of studies evaluating the prevalence of bacterial infections in disease exacerbation, this systematic review and meta-analysis was performed to determine the prevalence rate of bacterial infections in COPD patients.
PubMed, ISI Web of Science, and Scopus databases were systematically searched for population-based prevalence studies (1980–2018). MeSH terms for “Bacterial infections” and “AECOPD” were used as search keywords. The selected studies were filtered according to the inclusion and exclusion criteria. Fixed and random-effects models were used for estimation of summary effect sizes. Between-study heterogeneity, as well as publication bias, were calculated.
Finally, 118 out of 31,440 studies were selected. The overall estimation of the prevalence of bacterial infection was 49.59% [95% confidence interval (CI) 0.4418–0.55]. The heterogeneity in estimating the pooled prevalence of bacterial infections was shown in the studies (Cochran Q test: 6615, P
Gubareva L, Fry A.
Drug resistance is a topic of significant concern in the treatment of infectious diseases caused by rapidly evolving RNA viruses that can persist (eg, human immunodeficiency virus and hepatitis C virus) or reinfect (eg, influenza virus). Combination drug therapy is standard of care for the treatment of infections by rapidly mutating RNA viruses [1, 2]. However, it is not a common approach for treating influenza virus infections, partly because of the limited number of anti-influenza drugs and drug targets. We now know that all of the classes of anti-influenza drugs—M2 blockers, neuraminidase inhibitors (NAIs), and the newly licensed cap-dependent endonuclease inhibitor (baloxavir marboxil)—have low genetic barriers to resistance: 1 or 2 amino acid substitutions are sufficient to gain resistance [3, 4].
Keita Fukao, Yoshinori Ando, Takeshi Noshi, Mitsutaka Kitano, Takahiro Noda, Makoto Kawai, Ryu Yoshida, Akihiko Sato, Takao Shishido, Akira Naito
by Keita Fukao, Yoshinori Ando, Takeshi Noshi, Mitsutaka Kitano, Takahiro Noda, Makoto Kawai, Ryu Yoshida, Akihiko Sato, Takao Shishido, Akira Naito
Baloxavir marboxil (BXM) is an orally available small molecule inhibitor of cap-dependent endonuclease (CEN), an essential enzyme in the initiation of mRNA synthesis of influenza viruses. In the present study, we evaluated the efficacy of BXM against influenza virus infection in mouse models. Single-day oral administration of BXM completely prevented mortality due to infection with influenza A and B virus in mice. Moreover, 5-day repeated administration of BXM was more effective for reducing mortality and body weight loss in mice infected with influenza A virus than oseltamivir phosphate (OSP), even when the treatment was delayed up to 96 hours post infection (p.i.). Notably, administration of BXM, starting at 72 hours p.i. led to significant decrease in virus titers of >2-log10 reduction compared to the vehicle control within 24 hours after administration. Virus reduction in the lung was significantly greater than that observed with OSP. In addition, profound and sustained reduction of virus titer was observed in the immunocompromised mouse model without emergence of variants possessing treatment-emergent amino acid substitutions in the target protein. In our immunocompetent and immunocompromised mouse models, delayed treatment with BXM resulted in rapid and potent reduction in infectious virus titer and prevention of signs of influenza infection, suggesting that BXM could extend the therapeutic window for patients with influenza virus infection regardless of the host immune status.
Cécile Souty, Shirley Masse, Martine Valette, Sylvie Behillil, Isabelle Bonmarin, Cécile Pino, Clément Turbelin, Lisandru Capai, Ana-Maria Vilcu, Bruno Lina, Sylvie van der Werf, Thierry Blanchon, Alessandra Falchi, Thomas Hanslik
We aimed to identify patients’ clinical characteristics associated with respiratory viruses identified among patients presenting with influenza-like illness (ILI).
A. Chastagner et al.
Biofilm production by Haemophilus influenzae and Streptococcus pneumoniae has been implicated in the pathogenesis of otitis media, mainly in chronic and recurrent cases. We studied the “in vitro” biofilm production by these 2 species isolated alone or together from the nasopharynx of children with acute otitis media.
The studied strains were from 3 pneumococcal conjugate vaccine (PCV) periods: pre-PCV7, post-PCV7/pre-PCV13 and post-PCV13. A modified microtiter plate assay with crystal violet stain was used to study the biofilm production of 182 H. influenzae and 191 S. pneumoniae strains.
Overall, 117/181 (64.6%) H. influenzae and 128/191 (66.8%) S. pneumoniae strains produced biofilm. The proportion of biofilm-producing H. influenzae strains was greater with than without the isolation of S. pneumoniae in the same sample (75.5% vs 52.3%, p = 0.001). Conversely, the proportion of biofilm-producing S. pneumoniae strains was not affected by the presence or not of H. influenzae (66.3% vs 67.4%). S. pneumoniae serotypes 6B, 15B/C, 19A, 35F and 35B were the better biofilm producers (80%). Serotypes 11A, 14, 15A, 19F and 19A were more associated with H. influenzae biofilm-producing strains. Overall, 89/94 (94.6%) of cases with combined isolation showed biofilm production by S. pneumoniae or H. influenzae.
This study emphasizes the high proportion of biofilm production by H. influenzae and S. pneumoniae strains isolated from the nasopharynx of children with acute otitis media, which reinforces the results of studies suggesting the importance of biofilm in the pathogenesis of acute otitis media.
Budd A, Beacham L, Smith C, et al.
AbstractBackgroundThe evolution of influenza A viruses results in birth cohorts that have different initial influenza virus exposures. Historically, A/H3 predominant seasons have been associated with more severe influenza-associated disease; however, since the 2009 pandemic there are suggestions that some birth cohorts experience more severe illness in A/H1 predominant seasons.MethodsU.S. influenza virologic, hospitalization and mortality surveillance data during 2000-2017 were analyzed for cohorts born between 1918 and 1989 that likely had different initial influenza virus exposures based on viruses circulating during early childhood. Relative risk/rate during H3 compared to H1 predominant seasons during pre-pandemic versus pandemic and later periods were calculated for each cohort.ResultsDuring the pre-pandemic period, all cohorts had more influenza-associated disease during H3 predominant seasons than H1 predominant seasons. During the pandemic and later period, four cohorts had higher hospitalization and mortality rates during H1 predominant seasons than H3 predominant seasons.DiscussionBirth cohort differences in risk of influenza-associated disease by influenza A virus subtype can be seen in U.S. influenza surveillance data and differ between pre-pandemic and pandemic and later periods. As the population ages, the amount of influenza-associated disease may be greater in future H1 predominant seasons than H3 predominant seasons.
Neumann G, Kawaoka Y.
AbstractWorldwide outbreaks of influenza (pandemics) are caused by influenza A viruses to which people lack protective immune responses. Currently, we are unable to predict which influenza virus strains may cause a pandemic. Here, we summarize some of the information that will be needed to better assess the pandemic potential of influenza viruses, and we discuss our current gaps in knowledge.
Grazieli Maboni, Mauricio Seguel, Ana Lorton, Roy Berghaus, Susan Sanchez
by Grazieli Maboni, Mauricio Seguel, Ana Lorton, Roy Berghaus, Susan Sanchez
Canine infectious respiratory disease (CIRD) is a syndrome where multiple viral and bacterial pathogens are involved sequentially or synergistically to cause illness. There is limited information regarding the prevalence of pathogens related to CIRD in the United States as well as the role of co-infections in the pathogenesis of the syndrome. We aimed to conduct a comprehensive etiologic and epidemiologic study of multiple CIRD agents in a diverse dog population using molecular methods and statistical modeling analyses. In addition, a novel probe-based multiplex real-time PCR was developed to simultaneously detect and differentiate two species of Mycoplasma (M. canis and M. cynos). Canine adenovirus, canine distemper virus, canine parainfluenza virus, coronavirus, influenza A virus (H3N2 and H3N8), Bordetella bronchiseptica, M. canis, M. cynos and Streptococcus equi subsp. zooepidemicus were investigated in specimens from clinically ill and asymptomatic dogs received at the Athens Veterinary Diagnostic Laboratory. Results showed low occurrence of classical CIRD agents such as B. bronchiseptica, canine adenovirus and distemper virus, while highlighting the potential role of emerging bacteria such as M. canis and M. cynos. Statistical modeling analyses of CIRD pathogens emphasized the impact of co-infections on the severity of clinical presentation, and showed that host factors, such as animal age, are the most important predictors of disease severity. This study provides new insights into the current understanding of the prevalence and role of co-infections with selected viruses and bacteria in the etiology of CIRD, while underscoring the importance of molecular diagnosis and vaccination against this disease.
Skowronski D, De Serres G, Orenstein W.
We assessed the utility of a multi-target, real-time PCR assay for Bordetella pertussis detection and diagnosis in patients with severe respiratory illness (SRI), influenza-like illness (ILI), and asymptomatic controls.
Real-time PCR detection of IS481, pIS1001, hIS1001 and ptxS1 was performed on nasopharyngeal specimens (SRI, ILI and controls) and induced sputum (SRI) collected from June 2012 to May 2016 through respiratory illness surveillance. Using PCR cycle threshold (Ct) value cut-offs, IS481 positive cases were classified as confirmed (Ct
To improve national influenza vaccination recommendations, additional data on influenza A and B virus circulation are needed. Here, we describe the circulation of influenza A and B in the Czech Republic during 16 seasons.
This was a retrospective analysis of data collected from the 2000–2001 to 2015–2016 influenza seasons by the Czech Republic national influenza surveillance network. Influenza was confirmed and viral isolates subtyped by virological assays followed by antigen detection or by reverse transcriptase-polymerase chain reaction.
Of 16,940 samples collected, 5144 (30.4%) were influenza-positive. Influenza A represented 78.6% of positive cases overall and accounted for more than 55.0% of all influenza cases in every season, except for 2005–2006 (6.0%). Both A/H1N1 and A/H3N2 were detected in most seasons, except for 2001–2002 and 2003–2004 (only A/H3N2), and 2007–2008 and 2009–2010 (only A/H1N1). Influenza B represented 21.4% of positive cases overall (range, 0.0–94.0% per season). Both influenza B lineages were detected in three seasons, a single B lineage in 11, and no B strain in two. For the 11 seasons where influenza B accounted for ≥20% of positive cases, the dominant lineage was Yamagata in six and Victoria in four. In the remaining season, the two lineages co-circulated. For two seasons (2005–2006 and 2007–2008), the B lineage in the trivalent influenza vaccine did not match the dominant circulating B lineage.
In the Czech Republic, during the 2000–2001 to 2015–2016 influenza seasons, influenza virus circulation varied considerably. Although influenza A accounted for the most cases in almost all seasons, influenza B made a substantial, sometimes dominant, contribution to influenza disease.
A severe seasonal influenza epidemic was observed during 2017–2018 in China, prompting questions on clinical characteristics and outcomes of severe cases with influenza.
We retrospectively collected clinical data and outcomes of laboratory-confirmed hospitalized patients (severe to critical) during Jan-2011 to Feb-2018 from five hospitals, followed by a systematic analysis of cases from 2017 to 2018 (n = 289) and all previous epidemics during 2011–2017 (n = 169).
In-hospital fatality was over 5-folds higher during the 2017–2018 (p
Human parainfluenza virus (HPIV), usually combined with other pathogens, causes lower respiratory tract infection (LRTI) in children. However, clinical characteristics of HPIV coinfection with other pathogens were unclear. This study aimed to investigate the viral and atypical bacterial etiology of LRTI in children and compare the clinical characteristics of HPIV single infection with those of coinfection.
This study included 1335 patients, aged between 1 to 71 months, diagnosed with LRTI in Yuying Children's Hospital, Zhejiang, China, from December 2013 to June 2015. Nasopharyngeal secretions were collected, and respiratory pathogens were detected using Multiplex polymerase chain reaction. The clinical data of patients were collected and analyzed.
At least 1 pathogen was detected in 1181/1335 (88.5%) patients. The pathogens identified most frequently were respiratory syncytial virus, human rhinovirus, HPIV, adenovirus, and human metapneumovirus. The coinfection rate was 24.8%. HPIV coinfection with other viruses was more associated with running nose, shortness of breath, and oxygen support compared with HPIV single infection. Moreover, HPIV coinfection with atypical bacteria was more related to running nose, moist rales, and longer hospital duration compared with HPIV single infection, and also to longer hospital duration compared with coinfection with other viruses.
This study demonstrated that viral infections were highly associated with LRTI and the rate of coinfection was high. HPIV single infection was milder than coinfection with other viruses. Moreover, HPIV coinfection with atypical bacteria was more serious than HPIV single infection and coinfection with other viruses.
This article is protected by copyright. All rights reserved.
ter Horst L, Brouwer M, van der Ende A, et al.
AbstractBackgroundCerebrospinal fluid (CSF) leakage is a risk factor for developing bacterial meningitis.Materials/methodsWe analyzed episodes of community-acquired bacterial meningitis associated with CSF leakage from a prospective nationwide cohort study.ResultsCSF leakage was identified in 65 episodes of 2022 episodes (3%) in 53 patients. The cause of CSF leakage was identified in 49 of 65 episodes (75%), most and most commonly consisted of ear-nose-throat surgery (19 of 49 episodes [29%]) and remote head trauma (15 of 49 episodes [23%]). The episode was a recurrent meningitis episode in 38 patients (59%). Of the recurrent episodes, 27 had known CSF leakage (71%) of whom 20 (53%) had previous surgery aiming to close the leak. Nine patients (38%) with known CSF leakage had been vaccinated (23-valent pneumococcal vaccine in 9 patients, meningococcal serogroup C vaccine in 2, meningococcal serogroup A and Haemophilus influenzae type b vaccine each in 1 patient). Streptococcus pneumoniae was cultured in 33 episodes (51%) and H. influenzae in 11 episodes (17%). Most common pneumococcal serotype were 3 (4 episodes), 35B, 9N, 38 and 15C (each 2 episodes). H. influenzae was unencapsulated in all 10 episodes with known capsule type. The outcome was unfavorable in 8 episodes (12%) and no patient died.ConclusionBacterial meningitis in patients with CSF leakage have a high recurrence rate, despite surgical repair or vaccination, and outcome is generally favorable. CSF leakage should be suspected in patients with bacterial meningitis presenting with liquorrhoea, recurrent meningitis or with disease caused by H. influenzae.
Ison, M. G., Hirsch, H. H.
Patients undergoing solid-organ transplantation (SOT) or allogeneic hematopoietic cell transplantation (HCT) are at increased risk for infectious complications. Community-acquired respiratory viruses (CARVs) pose a particular challenge due to the frequent exposure pre-, peri-, and posttransplantation. Although influenza A and B viruses have a top priority regarding prevention and treatment, recent molecular diagnostic tests detecting an array of other CARVs in real time have dramatically expanded our knowledge about the epidemiology, diversity, and impact of CARV infections in the general population and in allogeneic HCT and SOT patients. These data have demonstrated that non-influenza CARVs independently contribute to morbidity and mortality of transplant patients. However, effective vaccination and antiviral treatment is only emerging for non-influenza CARVs, placing emphasis on infection control and supportive measures. Here, we review the current knowledge about CARVs in SOT and allogeneic HCT patients to better define the magnitude of this unmet clinical need and to discuss some of the lessons learned from human influenza virus, respiratory syncytial virus, parainfluenzavirus, rhinovirus, coronavirus, adenovirus, and bocavirus regarding diagnosis, prevention, and treatment.
Hsueh-Ju Chen, Chia-Ping Su, Ming-Tsan Liu, Tsung-Pei Tsou
Influenza B viruses can be divided into two antigenically and genetically distinct lineages, represented by B/Victoria/2/87 and B/Yamagata/16/88 viruses (Rota et al., 1990). These lineages have co-circulated since 2001 in variable, unpredictable proportions (Ray et al., 2017). In Taiwan, the two lineages of influenza B viruses evolved contemporaneously and independently (Yang et al., 2012; Kuo et al., 2016). Influenza B viruses are generally thought to affect a younger population and cause less severe illness than influenza A viruses (Chi et al., 2008; Caini et al., 2015; Jennings et al., 2018).
Influenza and pneumococcal vaccine uptake in the older population aged 65 years or over of Hong Kong dramatically increased since the 2003 SARS outbreak. This study is aimed to evaluate the impact of increased coverage of influenza and pneumococcal vaccines by comparing the change of disease burden in the older population of Hong Kong, with the burden in the older population of Brisbane with relatively high vaccine coverage in the past fifteen years.
Time series segmented regression models were applied to weekly numbers of cause-specific mortality or hospitalization of Hong Kong and Brisbane. Annual excess rates of mortality or hospitalization associated with influenza in the older population were estimated for the pre-SARS (reference period), post-SARS and post-pandemic period, respectively. The rate ratios (RRs) between these periods were also calculated to assess the relative change of disease burden.
Compared to the pre-SARS period, excess rates of mortality associated with influenza during the post-SARS period in Hong Kong decreased for cardiorespiratory diseases (RR = 0.90, 95% CI 0.80, 1.01), stroke (RR = 0.74, 95% CI 0.50, 1.09), and ischemic heart diseases (RR = 0.45, 95% CI 0.34, 0.58). The corresponding RRs in Brisbane were 0.79 (95% CI 0.54, 1.15), 0.33 (0.13, 0.80), and 1.09 (0.62, 1.90), respectively. Only the mortality of ischemic heart diseases showed a greater reduction in Hong Kong than in Brisbane. During the post-pandemic period, excess rates of all-cause mortality increased in Hong Kong, but to a lesser extent than in Brisbane (RR = 1.41 vs 2.39).
A relative decrease (or less of an increase) of influenza disease burden was observed in the older population of Hong Kong after increased coverage of influenza and pneumococcal vaccines in this population, as compared to those of Brisbane where vaccination rates remained stable. The lack of significant findings in some disease categories highlights the challenges of evaluating the benefits of vaccination at the population level.
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