Quantitative aspects of passive immunity to respiratory syncytial virus infection in infant cotton rats

The amount of passively acquired serum respiratory syncytial virus (RSV)-neutralizing antibodies required to protect the respiratory tract of cotton rats against infection was studied. Infant cotton rats were inoculated intraperitoneally with various dilutions of a single pool of sera derived from cotton rats convalescent from RSV infection. After 24 h, these animals were inoculated with RSV intranasally. Virus replication in the respiratory tract was suppressed in cotton rats which had a serum neutralizing antibody titer of 1:100 or greater. Resistance was greater in the lungs than in the nose. Complete or almost complete resistance in the lungs was observed in cotton rats with a serum neutralizing antibody titer of 1:380 or greater. The level of serum RSV-neutralizing antibodies required to confer significant resistance to infection in the cotton rat was similar to the level of maternally derived serum antibodies possessed by human infants less than 2 months of age, who as a group exhibit relative resistance to RSV disease compared with infants 2 to 6 months of age.     

Pathogenesis of adenovirus type 5 pneumonia in cotton rats (Sigmodon hispidus).

Cotton rats (Sigmodon hispidus) were inoculated intranasally with 10(2.0) to 10(10.0) PFU of human adenovirus type 5. The virus replicated to a high titer in pulmonary tissues, with the peak titer being proportional to the input dose. The 50% lethal dose was 10(9.4) PFU. Histopathologic changes were proportional to the infecting inoculum and included the infiltration of interstitial and intra-alveolar areas, moderate damage to bronchiolar epithelium, and cellular infiltration of peribronchiolar and perivascular regions. These changes could be divided into two phases: an early phase (affecting alveoli, bronchiolar epithelium, and peribronchiolar regions) with an infiltrate consisting primarily of monocytes-macrophages and neutrophils, with occasional lymphocytes, and a later phase (affecting peribronchiolar and perivascular regions) with an infiltrate consisting almost exclusively of lymphocytes. In both phases, the predominant process was the response of the host to infection, rather than direct viral damage to infected cells. An infecting inoculum of 10(8.0) PFU or larger caused severe damage to type II alveolar cells, which were swollen, showed a loss of lamellar bodies, and were surrounded by polymorphonuclear leukocytes and macrophages. No evidence of complete viral replication was found in type II alveolar cells.     

Expression of dengue virus structural proteins and nonstructural protein NS1 by a recombinant vaccinia virus.

A recombinant vaccinia virus containing cloned DNA sequences coding for the three structural proteins and nonstructural proteins NS1 and NS2a of dengue type 4 virus was constructed. Infection of CV-1 cells with this recombinant virus produced dengue virus structural proteins as well as the nonstructural protein NS1. These proteins were precipitated by specific antisera and exhibited the same molecular size and glycosylation patterns as authentic dengue virus proteins. Infection of cotton rats with the recombinant virus induced NS1 antibodies in 1 of 11 animals. However, an immune response to the PreM and E glycoproteins was not detected. A reduced level of gene expression was probably the reason for the limited serologic response to these dengue virus antigens.     

Effectiveness of topically administered neutralizing antibodies in experimental immunotherapy of respiratory syncytial virus infection in cotton rats.

Initial studies of the prophylactic effect of parenterally administered respiratory syncytial virus (RSV)-neutralizing antibodies in cotton rats indicated that virus replication in lung tissues was restricted when animals with preexisting antibody titers in serum of 1:100 or more (as measured by plaque reduction) were challenged intranasally with 10(4) PFU of virus. Subsequently, a therapeutic effect of parenterally administered RSV antibodies (present in human gamma globulin) was demonstrated in both cotton rats and owl monkeys. Parenteral inoculation of RSV-infected cotton rats or owl monkeys with purified human immunoglobulin licensed for intravenous administration in humans (IVIG) effected a 10(-1.7) to 10(-2.7) reduction in the level of pulmonary virus at the height of infection. Because of these encouraging results, we examined topical administration of IVIG to determine whether it was also effective and whether it offered an advantage over the parenteral route with regard to simplicity and the dose required for full therapeutic effect. IVIG (0.025 g/kg) administered topically by the intranasal route to anesthetized cotton rats at the height of RSV infection effected a 10(2.2)-fold reduction in viral titers of pulmonary tissues and a complete clearance of detectable virus in 92% of the animals within 24 h. In contrast, 4 g of IVIG per kg was required to produce a comparable therapeutic effect when the material was administered parenterally. Thus, the therapeutic effect of IVIG was 160 times greater by the topical route than by parenteral inoculation.     

Psychological distress,resettlement stress,and lower school engagement among Arabic-speaking refugee parents in Sydney,Australia: A cross-sectional cohort study

BackgroundSchools play a key role in supporting the well-being and resettlement of refugee children, and parental engagement with the school may be a critical factor in the process. Many resettlement countries have policies in place to support refugee parents’ engagement with their children’s school. However, the impact of these programs lacks systematic evaluation. This study first aimed to validate self-report measures of parental school engagement developed specifically for the refugee context, and second, to identify parent characteristics associated with school engagement, so as to help tailor support to families most in need.Methods and findingsThe report utilises 2016 baseline data of a cohort study of 233 Arabic-speaking parents (77% response rate) of 10- to 12-year-old schoolchildren from refugee backgrounds across 5 schools in Sydney, Australia. Most participants were born in Iraq (81%) or Syria (11%), and only 25% spoke English well to very well. Participants’ mean age was 40 years old, and 83% were female. Confirmatory factor analyses were run on provisional item sets identified from a literature review and separate qualitative study. The findings informed the development of 4 self-report tools assessing parent engagement with the school and school community, school belonging, and quality of the relationship with the schools’ bilingual cultural broker. Cronbach alpha and Pearson correlations with an established Teacher–Home Communication subscale demonstrated adequate reliability (α = 0.67 to 0.80) and construct and convergent validity of the measures (p < 0.01), respectively.Parent characteristics were entered into respective least absolute shrinkage and selection operator (LASSO) regression analyses. The degree of parents’ psychological distress (as measured by the Kessler10 self-report instrument) and postmigration living difficulties (PLMDs) were each associated with lower school engagement and belonging, whereas less time lived in Australia, lower education levels, and an unemployed status were associated with higher ratings in relationship quality with the schools’ cultural broker. Study limitations include the cross-sectional design and the modest amount of variance (8% to 22%) accounted for by the regression models.ConclusionsThe study offers preliminary refugee-specific measures of parental school engagement. It is expected they will provide a resource for evaluating efforts to support the integration of refugee families into schools. The findings support the need for initiatives that identify and support parents with school-attending children from refugee backgrounds who are experiencing psychological distress or resettlement stressors. At the school level, the findings suggest that cultural brokers may be effective in targeting newly arrived families.

Jess Baker and co-workers study engagement of Arabic-speaking refugees with their children’s schools in Australia.     

Enhancement of respiratory syncytial virus pulmonary pathology in cotton rats by prior intramuscular inoculation of formalin-inactiva ted virus.

Cotton rats previously inoculated with Formalin-inactivated respiratory syncytial virus (RSV) were challenged intranasally with live RSV to induce an enhancement of RSV disease similar to that observed after the administration of Formalin-inactivated RSV vaccine to human infants 20 years ago. Within 24 h after infection with RSV, cotton rats developed pulmonary lesions that reached a maximum by day 4. Histologically, the lesions resembled an experimental pulmonary Arthus reaction. An action of Formalin on RSV appears to be responsible for this effect, because live virus or virus heated in the absence of Formalin did not induce enhanced immunopathology. Selected epitopes on the fusion (F) or attachment (G) or both RSV surface glycoproteins that are involved in inducing neutralizing antibodies were modified to reduce or ablate their antigenicity. However, other epitopes on the F or G or both glycoproteins were not ablated by Formalin, because cotton rats inoculated parenterally with a Formalin-inactivated virus developed a high level of F and G antibodies measurable by an enzyme-linked immunosorbent assay. At this time, the effect of Formalin on RSV cannot be localized to either the F or G glycoprotein of RSV.     

Mechanism of antibody-mediated viral clearance in immunotherapy of respiratory syncytial virus infection of cotton rats.

Antibody-mediated clearance of respiratory syncytial virus from cotton rat pulmonary tissues occurs in the absence of complement and in the absence of the Fc portion of the immunoglobulin G molecule, suggesting that complement-independent, cell-independent neutralization is the major mechanism of clearance.