The Laminin Interactome: A Multifactorial Laminin-Binding Strategy by Nontypeable Haemophilus influenzae for Effective Adherence and Colonization

By Yu-Ching Su,  Emma Mattsson,  Birendra Singh,  Farshid Jalalvand,  Timothy F Murphy, Kristian Riesbeck

The Journal of Infectious Diseases, To be published September 15, 2019

 

Laminin is a well-defined component of the airway basement membrane (BM). Efficient binding of laminin via multiple interactions is important for nontypeable Haemophilus influenzae (NTHi) colonization in the airway mucosa. In this study, we identified elongation factor thermo-unstable (EF-Tu), l-lactate dehydrogenase (LDH), protein D (PD), and peptidoglycan-associated lipoprotein P6 as novel laminin-binding proteins (Lbps) of NTHi. In parallel with other well-studied Lbps (protein 4 [P4], protein E [PE], protein F [PF], and Haemophilus adhesion and penetration protein [Hap]), EF-Tu, LDH, PD, and P6 exhibited interactions with laminin, and mediated NTHi laminin-dependent adherence to pulmonary epithelial cell lines. More importantly, the NTHi laminin interactome consisting of the well-studied and novel Lbps recognized laminin LG domains from the subunit α chains of laminin-111 and -332, the latter isoform of which is the main laminin in the airway BM. The NTHi interactome mainly targeted multiple heparin-binding domains of laminin. In conclusion, the NTHi interactome exhibited a high plasticity of interactions with different laminin isoforms via multiple heparin-binding sites.

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Dual and Triple Infections With Influenza A and B Viruses: A Case-Control Study in Southern Brazil

By Tatiana Schäffer Gregianini,  Ivana R Santos Varella,  Patricia Fisch,  Letícia Garay Martins, Ana B G Veiga

The Journal of Infectious Diseases, To be published September 15, 2019

 

Influenza surveillance is important for disease control and should consider possible coinfection with different viruses, which can be associated with disease severity. This study analyzed 34 459 patients with respiratory infection from 2009 to 2018, of whom 8011 were positive for influenza A virus (IAV) or influenza B virus (IBV). We found 18 cases of dual influenza virus infection, including coinfection with 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09) and influenza A(H3N2) virus (1 case), A(H1N1)pdm09 and IBV (6 cases), A(H3N2) and IBV (8 cases), and nonsubtyped IAV and IBV (3 cases); and 1 case of triple infection with A(H3N2), A(H1N1)pdm09, and IBV. Compared with 76 monoinfected patients, coinfection was significantly associated with cardiopathy and death. Besides demographic characteristics and clinical symptoms, we assessed vaccination status, antiviral treatment, timeliness of antiviral use, hospitalization, and intensive care unit admission, but no significant differences were found between coinfected and monoinfected cases. Our findings indicate that influenza virus coinfection occurs more often than previously reported and that it can lead to a worse disease outcome.

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Association of Age at First Severe Respiratory Syncytial Virus Disease With Subsequent Risk of Severe Asthma: A Population-Based Cohort Study

By Nusrat Homaira,  Nancy Briggs,  Ju-Lee Oei,  Lisa Hilder,  Barbara Bajuk,  Adam Jaffe, Saad B Omer

The Journal of Infectious Diseases, August 15, 2019

 

In a population-based cohort study, we determined the association between the age at first severe respiratory syncytial virus (RSV) disease and subsequent asthma.

Incidence rates and rate ratios of the first asthma-associated hospitalization after 2 years of age in children hospitalized for RSV disease at <3 months, 3 to <6 months, 6 to <12 months, and 12–24 months of age were calculated.

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Double-Edged Role of Interleukin 17A in Streptococcus pneumoniae Pathogenesis During Influenza Virus Coinfection

By Ganesh Ambigapathy,  Taylor Schmit,  Ram Kumar Mathur,  Suba Nookala,  Saad Bahri, Liise-anne Pirofski,  M Nadeem Khan

The Journal of Infectious Diseases, September 1, 2019

 

We sought to determine the role of host interleukin 17A (IL-17A) response against colonizing Streptococcus pneumoniae, and its transition to a pathogen during coinfection with an influenza virus, influenza A H1N1 A/Puerto Rico/8/1934 (PR8).

Wild-type (WT) C57BL/6 mice were intranasally inoculated with S. pneumoniae serotype 6A to establish colonization and later infected with the influenza strain, PR8, resulting in invasive S. pneumoniae disease. The role of the IL-17A response in colonization and coinfection was investigated in WT, RoRγt−/− and RAG1−/− mice with antibody-mediated depletion of IL-17A (WT) and CD90 cells (RAG1−/−).

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Exploratory meeting to review new evidence for Integrated Management of Childhood Illness (IMCI) danger signs

The World Health Organization, August 1, 2019

 

For children up to 5 years of age with common childhood illnesses, WHO’s IMCI strategy recommends using clinical signs for diagnosis, treatment and place-of-treatment decisions. In order to increase access to pneumonia treatment, in 2014 WHO revised pneumonia management guidance within IMCI. It now recommends that lower chest indrawing, which previously required hospitalization along with other referral clinical signs considered as danger signs for injectable antibiotics, be treated with oral amoxicillin on an outpatient basis in settings with low HIV prevalence. These danger signs include convulsions; unable to drink; unconscious or drowsy; vomiting everything; stiff neck; severe dehydration; stridor in a calm child; oedema on both feet; weight for height (WHZ) Z-score less than - 3 SD or mid-upper arm circumference (MUAC) less than 115 mm; severe palmar pallor; clouding of the cornea in a child with measles, and tender swelling behind the ear in a child with an ear problem.

However, a recent retrospective analysis of data from hospitalized children in Kenya showed that mortality was high among children with mild to moderate palmar pallor, WAZ less than - 3 SD and lower chest indrawing. This finding raised concerns that these children should be treated on an inpatient basis despite the revised guidelines. In order to evaluate the implications of this new evidence and other data and to identify questions for future research, a two-day exploratory meeting of pneumonia research experts, epidemiologists and child health specialists/paediatricians from a range of countries with varying resources was convened in Geneva, Switzerland, on 4–5 September 2018.

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