Epidemiology and risk factors of respiratory syncytial virus associated acute respiratory tract infection in hospitalized children younger than 5 years from Sri Lanka.

Background: Respiratory syncytial virus (RSV) is the leading cause of acute respiratory tract infections (ARTI) and a major cause of morbidity and mortality in children worldwide. Aim: This study aimed to describe the prevalence and seasonal patterns of RSV and to determine the actual and predictive association of RSV-associated ARTI and clinical, socio-demographic, and climatic risk factors in children < 5 years. Methods: Nasopharyngeal aspirates were collected from 500 children < 5 years admitted to the Kegalle General Hospital, Sri Lanka between May 2016 to July 2018. RSV and RSV subtypes were detected using immunofluorescence assay and real time RT-PCR, respectively. Descriptive and inferential statistics were done for the data analysis using Chi-square, Fisher's exact, Kruskal-Wallis test, and multiple binary logistic regression in the statistical package for social sciences (SPSS), version 16.0. Results: Prevalence of RSV-associated ARTI was 28% in children < 5 years. Both RSV subtypes were detected throughout the study period. RSV-B was the dominant subtype detected with a prevalence of 72.14%. RSV infection in general caused severe respiratory disease leading to hypoxemia. Compared to RSV-B, RSV-A infection had more symptoms leading to hypoxemia. Factors increasing the risk of contracting RSV infection included number of people living (n > 6), having pets at home and inhaling toxic fumes. The inferential analysis predicts RSV infection in children < 5 years with ARTI, with a 75.4% probability with clinical and socio-demographic characteristics like age < 1 year, fever for > 4 days, cough, conjunctivitis, stuffiness, fatigue, six or more people at home, having pets at home and inhaling toxic fumes. Climatic factors like increases in temperature (°C), wind speed (Km/h), wind gust (Km/h), rainfall (mm) and atmospheric pressure (mb) showed a strong correlation with the RSV infection in children.

Identifying the research, advocacy, policy and implementation needs for the prevention and management of respiratory syncytial virus lower respiratory tract infection in low- and middle-income countries.

Introduction: The high burden of respiratory syncytial virus (RSV) infection in young children disproportionately occurs in low- and middle-income countries (LMICs). The PROUD (Preventing RespiratOry syncytial virUs in unDerdeveloped countries) Taskforce of 24 RSV worldwide experts assessed key needs for RSV prevention in LMICs, including vaccine and newer preventive measures. Methods: A global, survey-based study was undertaken in 2021. An online questionnaire was developed following three meetings of the Taskforce panellists wherein factors related to RSV infection, its prevention and management were identified using iterative questioning. Each factor was scored, by non-panellists interested in RSV, on a scale of zero (very-low-relevance) to 100 (very-high-relevance) within two scenarios: (1) Current and (2) Future expectations for RSV management. Results: Ninety questionnaires were completed: 70 by respondents (71.4% physicians; 27.1% researchers/scientists) from 16 LMICs and 20 from nine high-income (HI) countries (90.0% physicians; 5.0% researchers/scientists), as a reference group. Within LMICs, RSV awareness was perceived to be low, and management was not prioritised. Of the 100 factors scored, those related to improved diagnosis particularly access to affordable point-of-care diagnostics, disease burden data generation, clinical and general education, prompt access to new interventions, and engagement with policymakers/payers were identified of paramount importance. There was a strong need for clinical education and local data generation in the lowest economies, whereas upper-middle income countries were more closely aligned with HI countries in terms of current RSV service provision. Conclusion: Seven key actions for improving RSV prevention and management in LMICs are proposed.

Clinical and epidemiological characteristics of influenza virus infection in hospitalized children with acute respiratory infections in Sri Lanka.

Influenza viruses (Inf-V) are an important cause of acute respiratory infection (ARI) in children. This study was undertaken to describe the clinical and epidemiological characteristics of Inf-V infections in a sample of hospitalized children with ARI. Nasopharyngeal aspirates (NPA) from 500 children between 1 month to 5 years old with symptoms of ARI were collected at the Teaching Hospital Kegalle Sri Lanka From May 2016 to June 2018, NPAs were tested for influenza A (Inf-A) and B (Inf-B) viruses, human respiratory syncytial virus (hRSV), human parainfluenza virus (hPIV) 1-3 using an immunofluorescence assay. The Inf-V were then subtyped using a multiplex RT-PCR. Inf-V were detected in 10.75% (54/502) of the hospitalized children with ARI and in that 5.57% (28/502) were positive for Inf-A and 5.17% (26/502) were positive for Inf-B. Of the 54 Inf-V positive children, 33 were aged between 6 and 20 months. Of the 28 children infected with Inf-A, 15 had uncharacterized lower respiratory infection, 7 had bronchopneumonia and 6 had bronchiolitis. Of the 26 children infected with Inf-B, 11 had uncharacterized lower respiratory infection, 10 had bronchiolitis, and 4 had bronchopneumonia. Inf-B circulated throughout the year with a few peaks, one in June and then in August followed by November to December in 2016 and one in April 2017 and January 2018. Inf-A circulated throughout the year with a major peak in March to April 2017 and July 2018. ARI was more common in boys compared to girls. Majority of the children infected with Inf-V were diagnosed with uncharacterized lower respiratory infection and mild to moderate bronchiolitis. Inf-V infections were prevalent throughout the year in the study area of Sri Lanka with variations in the type of the circulating virus.

Group A streptococcal antigen exposed rat model to investigate neurobehavioral and cardiac complications associated with post-streptococcal autoimmune sequelae.

Background: The neuropsychiatric disorders due to post-streptococcal autoimmune complications such as Sydenham's chorea (SC) are associated with acute rheumatic fever and rheumatic heart disease (ARF/RHD). An animal model that exhibits characteristics of both cardiac and neurobehavioral defects in ARF/RHD would be an important adjunct for future studies. Since age, gender, strain differences, and genotypes impact on the development of autoimmunity, we investigated the behavior of male and female Wistar and Lewis rat strains in two age cohorts (<6 weeks and >12 weeks) under normal husbandry conditions and following exposure to group A streptococcus (GAS). Methods: Standard behavioral assessments were performed to determine the impairments in fine motor control (food manipulation test), gait and balance (beam walking test), and obsessive-compulsive behavior (grooming and marble burying tests). Furthermore, electrocardiography, histology, and behavioral assessments were performed on male and female Lewis rats injected with GAS antigens. Results: For control Lewis rats there were no significant age and gender dependent differences in marble burying, food manipulation, beam walking and grooming behaviors. In contrast significant age-dependent differences were observed in Wistar rats in all the behavioral tests except for food manipulation. Therefore, Lewis rats were selected for further experiments to determine the effect of GAS. After exposure to GAS, Lewis rats demonstrated neurobehavioral abnormalities and cardiac pathology akin to SC and ARF/RHD, respectively. Conclusion: We have characterised a new model that provides longitudinal stability of age-dependent behavior, to simultaneously investigate both neurobehavioral and cardiac abnormalities associated with post-streptococcal complications.

In Search of the Holy Grail: A Specific Diagnostic Test for Rheumatic Fever.

Current diagnosis of Acute Rheumatic Fever and Rheumatic Heart Disease (ARF/RHD) relies on a battery of clinical observations aided by technologically advanced diagnostic tools and non-specific laboratory tests. The laboratory-based assays fall into two categories: those that (1) detect "evidence of preceding streptococcal infections" (ASOT, anti-DNAse B, isolation of the Group A Streptococcus from a throat swab) and (2) those that detect an ongoing inflammatory process (ESR and CRP). These laboratory tests are positive during any streptococcal infection and are non-specific for the diagnosis of ARF/RHD. Over the last few decades, we have accumulated considerable knowledge about streptococcal biology and the immunopathological mechanisms that contribute to the development, progression and exacerbation of ARF/RHD. Although our knowledge is incomplete and many more years will be devoted to understanding the exact molecular and cellular mechanisms involved in the spectrum of clinical manifestations of ARF/RHD, in this commentary we contend that there is sufficient understanding of the disease process that using currently available technologies it is possible to identify pathogen associated peptides and develop a specific test for ARF/RHD. It is our view that with collaboration and sharing of well-characterised serial blood samples from patients with ARF/RHD from different regions, antibody array technology and/or T-cell tetramers could be used to identify streptococcal peptides specific to ARF/RHD. The availability of an appropriate animal model for this uniquely human disease can further facilitate the determination as to whether these peptides are pathognomonic. Identification of such peptides will also facilitate testing of potential anti-streptococcal vaccines for safety and avoid potential candidates that may pre-dispose potential vaccine recipients to adverse outcomes. Such peptides can also be readily incorporated into a universally affordable point of care device for both primary and tertiary care.

Requirements for a Robust Animal Model to Investigate the Disease Mechanism of Autoimmune Complications Associated With ARF/RHD.

The pathogenesis of Acute Rheumatic Fever/Rheumatic Heart Disease (ARF/RHD) and associated neurobehavioral complications including Sydenham's chorea (SC) is complex. Disease complications triggered by Group A streptococcal (GAS) infection are confined to human and determining the early events leading to pathology requires a robust animal model that reflects the hallmark features of the disease. However, modeling these conditions in a laboratory animal, of a uniquely human disease is challenging. Animal models including cattle, sheep, pig, dog, cat, guinea pigs rats and mice have been used extensively to dissect molecular mechanisms of the autoimmune inflammatory responses in ARF/RHD. Despite the characteristic limitations of some animal models, several rodent models have significantly contributed to better understanding of the fundamental mechanisms underpinning features of ARF/RHD. In the Lewis rat autoimmune valvulitis model the development of myocarditis and valvulitis with the infiltration of mononuclear cells along with generation of antibodies that cross-react with cardiac tissue proteins following exposure to GAS antigens were found to be similar to ARF/RHD. We have recently shown that Lewis rats injected with recombinant GAS antigens simultaneously developed cardiac and neurobehavioral changes. Since ARF/RHD is multifactorial in origin, an animal model which exhibit the characteristics of several of the cardinal diagnostic criteria observed in ARF/RHD, would be advantageous to determine the early immune responses to facilitate biomarker discovery as well as provide a suitable model to evaluate treatment options, safety and efficacy of vaccine candidates. This review focuses on some of the common small animals and their advantages and limitations.

A review on disease burden and epidemiology of childhood parainfluenza virus infections in Asian countries.

Human parainfluenza viruses (HPIVs) are an important cause of acute respiratory tract infections (ARTIs) in children less than 5 years, second only to human respiratory syncytial viruses (HRSVs). Generally, patients infected with HPIVs are treated in outpatient clinics, yet also contribute to ARTI-associated hospitalization in children. Although HPIV infections are well studied in developed countries, these infections remain under-investigated and not considered in the routine laboratory diagnosis of childhood ARTI in many developing countries in Asia. We performed an extensive literature search on the prevalence, epidemiology, and burden of HPIV infections in children less than 5 years in Asia using PubMed and PubMed Central search engines. Based on the literature, the prevalence of HPIV infection in Asia ranges from 1% to 66%. According to many studies, HPIV-3 is the major virus circulating among children; however, several studies failed to detect HPIV-4 due to unavailability of diagnostic tools. In Asian countries, HPIV contributes a substantial disease burden in children. The data in this review should assist researchers and public health authorities to plan preventive measures, including accelerating research on vaccines and antiviral drugs.

A review on epidemiology and impact of human metapneumovirus infections in children using TIAB search strategy on PubMed and PubMed Central articles.

Acute respiratory tract infections (ARTI) contribute to morbidity and mortality in children globally. Viruses including human metapneumovirus (hMPV) account for most ARTIs. The virus causes upper and lower respiratory tract infections mostly in young children and contributes to hospitalization of individuals with asthma,chronic obstructive pulmonary diseases and cancer. Moreover, hMPV pauses a considerable socio-economic impact creating a substantial disease burden wherever it has been studied, although hMPV testing is relatively new in many countries. We aimed to comprehensively analyze the epidemiological aspects including prevalence, disease burden and seasonality of hMPV infections in children in the world. We acquired published data extracted from PubMed and PubMed Central articles using the title and abstract (TIAB)search strategy for the major key words on hMPV infections from 9/54 African, 11/35 American, 20/50 Asian, 2/14 Australian/Oceanian and 20/51 European countries. According to the findings of this review, the prevalence of hMPV infection ranges from 1.1 to 86% in children of less than 5 years of age globally. Presence of many hMPV genotypes (A1, A2, B1, B2) and sub-genotypes (A2a, A2b, A2c, B2a, B2b) suggests a rapid evolution of the virus with limited influence by time and geography. hMPV infection mostly affects children between 2 to 5 years of age. The virus is active throughout the year in the tropics and epidemics occur during the winter and spring in temperate climates, contributing to a substantial disease burden globally.