18-month longitudinal SARS COV-2 neutralizing antibody dynamics in haemodialysis patients receiving heterologous 3-dose vaccination (AZD-1222- AZD-1222- BNT162b2) in a lower middle income setting.

BACKGROUND: Patients with chronic kidney disease on haemodialysis (HD) were given priority COVID-19 vaccination due to increased disease risk. The immune response to COVID-19 vaccination in patients on HD was diminished compared to healthy individuals in 2-dose studies. This study aimed to evaluate seroconversion rate, neutralizing antibody (nAB) levels and longitudinal antibody dynamics to 3-dose heterologous vaccination against COVID-19 in a cohort of HD patients compared to healthy controls and assess patient factors associated with antibody levels. METHODS: This study was a case-control longitudinal evaluation of nAB dynamics in 74 HD patients compared to 37 healthy controls in a low/middle income setting. Corresponding samples were obtained from the two cohorts at time-points (TP) 1-1-month post 2nd dose of AZD1222 vaccine, TP2- 4 months post 2nd dose, TP4- 2 weeks post 3rd dose with BNT162b2 vaccine, TP5-5 months post 3rd dose and TP6-12 months post 3rd dose. Additional data is available at TP0- pre 2nd dose and TP3- 6 months post 2nd dose in HC and HD cohorts respectively. Anti-SARS-CoV-2 nAB were detected using Genscript cPassTM pseudoviral neutralization kit. Demographic and clinical details were obtained using an interviewer administered questionnaire. RESULTS: Cohorts were gender matched while mean age of the HD cohort was 54.1yrs (vs HCs mean age, 42.6yrs, p < 0.05). Percentage seroconverted and mean/median antibody level (MAB) in the HD cohort vs HCs at each sampling point were, TP1-83.7% vs 100% (p < 0.05), MAB-450 IU/ml vs 1940 IU/ml (p < 0.0001); TP2-71.4% vs 100%, (p < 0.001), MAB- 235 IU/ml vs 453 IU/ml, (p < 0.05); TP4-95.2% vs 100% (p > 0.05), MAB-1029 IU/ml vs 1538 IU/ml (p < 0.0001); TP5-100% vs 100%, MAB-1542 IU/ml vs 1741IU/ml (p > 0.05); TP6-100% vs 100%, MAB-1961 IU/ml vs 2911 IU/ml (p > 0.05). At TP2, patients aged < 60 years (p < 0.001) were associated with maintaining seropositivity compared to patients > 60 years. CONCLUSION: Two dose vaccination of haemodialysis patients provided poor nAB levels which improved markedly following 3rd dose vaccination, the effect of which was long- lasting with high nAB levels in both patients and controls detectable at 1 year follow-up.

Quality of the sample-based RNA determines the real-time RT-PCR results in the laboratory diagnosis of COVID-19.

Effect of the quality of sample-based RNA on COVID-19 real-time RT-PCR results was investigated. The purity of the extracts was dependent on the extraction method (P<0.0001) and affected the test interpretations (P = 0.002). Gross RNA concentration negatively correlated with Ct values (P < 0.0001). The presence of impurities contributed to inconclusive test results.

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.

Demographic and clinical characteristics of human bocavirus-1 infection in patients with acute respiratory tract infections during the COVID-19 pandemic in the Central Province of Sri Lanka.

BACKGROUND: Human bocavirus-1 (hBoV-1) was first detected in respiratory specimens in 2005. Due to high co-infection rates and prolonged shedding of the virus, the pathogenic role of hBoV-1 as a primary causative agent of respiratory infections is still under discussion. This study aimed to determine the prevalence of hBoV-1 infection in patients with acute respiratory tract infections (ARTIs) during the COVID-19 pandemic in the Central Province of Sri Lanka. METHODS: A total of 1021 patients (Age 12 days to ≤ 85 years) with ARTI symptoms including fever, cough, cold, sore throat and shortness of breath within first 7 days of the illness were included. The study was carried out at the National Hospital, Kandy, Sri Lanka from January 2021 to October 2022. Respiratory specimens were tested to detect 23 pathogens including hBoV-1 using a real time PCR. Prevalence of hBoV-1 co-infections with other respiratory pathogens and distribution of hBoV-1 infection among different age groups were determined. Moreover, clinical and demographic characteristics of hBoV-1 mono-infection associated ARTI were compared with that of the hBoV-1 co-infections. RESULTS: Respiratory infections were detected in 51.5% (526/1021) of the patients and of these 82.5% were mono- and 17.1% were co-infections. hBoV-1 was detected in 66 patients and this was the most prevalent respiratory virus associated with 40% co-infections. Of the 66 hBoV-1 positive patients, 36 had co-infections and of these 33 had dual and 3 had triple infections. Most of the hBoV-1 co-infections were identified in children aged 2-<5 years. hBoV-1 co-infections were most frequently detected with respiratory syncytial virus (RSV) and Rhino/ Entero viruses (Rh/EnV). No differences were observed in age, gender and clinical presentations in those with hBoV-1 mono- compared to co-infections. Intensive care admissions were less among hBoV-1 mono-infected than hBoV-1 co-infected patients. CONCLUSION: This study shows a prevalence of 12.5% for hBoV-1 infections in patients with ARTI. RSV and Rh/EnV were the most common co-infecting pathogens with hBoV-1. Clinical features of hBoV-1 mono-infections were not different to that of the hBoV-1 co-infections. Interactions between hBoV-1 and other respiratory pathogens need investigation to identify the role of hBoV-1 in clinical severity of co-infections.

Characteristics of the initial dengue outbreaks in a region without dengue prior to mid-2009 in a dengue-endemic country.

INTRODUCTION: The present study evaluated the characteristics of the initial dengue outbreaks in the Jaffna peninsula, a region without dengue prior to mid-2009 in dengue-endemic Sri Lanka, a tropical island nation. METHODOLOGY: This is a cross-sectional study conducted using a total of 765 dengue patients' clinical data and samples collected from the Teaching Hospital, Jaffna during the initial dengue outbreaks. Clinical, non-specific, and specific virological laboratory characteristics including the platelet count, NS1 antigen, and anti-DENV IgM/IgG were evaluated as correlates of dengue virus (DENV) infection in the two initial outbreaks of 2009/2010 and 2011/2012 in Northern Sri Lanka. RESULTS: Firstly, affected age and clinical characteristics were significantly different between the outbreaks (p < 0.005). Secondly, NS1 antigen detection in patients with fever days < 5 was statistically significant (p < 0.005). Thirdly, platelet count, detection of NS1 antigen, and anti-DENV IgM/IgG profiles were adequate to diagnose 90% of the patients; hepatomegaly and platelet count of < 25,000/mm3 were identified as predictors of severe disease. Fourthly, secondary DENV infections were detected in the early stages of the illness in many patients. Finally, infecting DENV serotypes were different between the two outbreaks. CONCLUSIONS: Clinical and non-specific laboratory characteristics and the infecting DENV serotypes between the two initial outbreaks in Northern Sri Lanka were significantly different. NS1 antigen, anti-DENV IgM/IgG, and platelet counts were identified 90% of the dengue patients. Hepatomegaly and platelet count of < 25,000/mm3 were able to predict the disease severity in this study.

Relationship between clinical and laboratory features with infecting dengue virus serotypes in a sample of dengue suspected adult patients from 2015-2017 in Sri Lanka.

Dengue is a major viral disease affecting the tropics. Although previous research has focused on the relationship between the infecting dengue virus (DENV) serotypes and disease severity, less work has been done on the relationship between the clinical and laboratory features and the infecting DENV serotypes in Sri Lanka. We evaluated the relationship between the clinical and laboratory features and the infecting DENV serotypes in adult patients with clinically suspected dengue admitted to the Base Hospital, Mawanella, Sri Lanka from December 2015 to March 2017. Blood samples of 200 dengue suspected patients were tested for the infecting DENV serotypes using a reverse transcription polymerase chain reaction with primers targeting the envelope region of the virus. Relationship between the infecting DENV serotypes with clinical and laboratory features was assessed using Z score and paired t tests. Of the 200 patients tested, 39 (19.5%) were positive for DENV, any of the four DENV serotypes alone or in combination. The highest number of infections was noted with DENV-2 (n=18, 46.1%). Fever (P=0.000) and rash (P=0.017) were frequently noted in DENV negative patients while bleeding (P=0.012) was more frequently noted in DENV serotype positive patients. Platelet count of <100,000 µl-1 was significantly associated with DENV serotype positivity (P=0.000). Platelet count of <100,000 µl-1 (P=0.035) and haemoglobin (Hb) of >13mgdl-1 (P=0.016) were noted in 15 of the 18 DENV-2 positive patients. Clinical and laboratory features of severe dengue with bleeding manifestations, low platelet counts and high Hb were noted in DENV-2 infections.

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.

Pre-vaccination RT-PCR negative contacts in workplace settings show high, SARS COV-2 neutralizing antibody levels.

BACKGROUND: Asymptomatic SARS-CoV-2 infection occurring in RT-PCR negative individuals represent a poorly characterized cohort with important infection control connotations. While household and community-based studies have evaluated seroprevalence of antibody and transmission dynamics in this group, workplace-based data is currently unavailable. METHODS: A cohort study was carried out in July 2021, during and immediately following the peak of the 3rd wave of COVID-19 in Sri Lanka, prior to mass vaccination. A total of 92 unvaccinated individuals between the ages of 17-65 years were purposively sampled from an office and two factory settings. The selected cohort that had been exposed to RT-PCR positive cases in the workplace was tested RT-PCR negative. Serological samples collected six weeks post exposure were tested for anti-SARS-CoV-2 neutralizing antibody. RESULTS: The seroprevalence for SARS-CoV-2 specific neutralizing antibodies in the overall cohort was 63.04% (58/92). Seroprevalences in the office setting, factory setting 1 and factory setting 2 were 69.2% (9/13), 55.7% (34/61) and 83.33% (15/18), respectively. Primary risk factor associated with seropositivity was face to face contact with no mask for > 15 min (p < 0.024, Odds Ratio (OR); 5.58, 95%CI;1.292- 25.65). Individuals with workspace exposure had significantly higher levels of neutralizing antibodies than those who did not (percentage neutralization in assay 63.3% (SD:21)vs 45.7% (SD:20), p = 0.0042), as did individuals who engaged socially without protective measures (62.4 (SD:21.6)% vs 49.7 (SD:21)%, p = 0.026). CONCLUSION: There was a high seroprevalence for SARS-CoV-2 specific neutralizing antibodies among RT-PCR negative contacts in workplace settings in Sri Lanka. Higher levels of transmission of SARS-CoV-2 infection than estimated based on RT-PCR positive contact data indicate need for targeted infection control measures in these settings during future outbreaks.

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.

Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in children younger than 5 years in 2019: a systematic analysis.

BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infection in young children. We previously estimated that in 2015, 33·1 million episodes of RSV-associated acute lower respiratory infection occurred in children aged 0-60 months, resulting in a total of 118 200 deaths worldwide. Since then, several community surveillance studies have been done to obtain a more precise estimation of RSV associated community deaths. We aimed to update RSV-associated acute lower respiratory infection morbidity and mortality at global, regional, and national levels in children aged 0-60 months for 2019, with focus on overall mortality and narrower infant age groups that are targeted by RSV prophylactics in development. METHODS: In this systematic analysis, we expanded our global RSV disease burden dataset by obtaining new data from an updated search for papers published between Jan 1, 2017, and Dec 31, 2020, from MEDLINE, Embase, Global Health, CINAHL, Web of Science, LILACS, OpenGrey, CNKI, Wanfang, and ChongqingVIP. We also included unpublished data from RSV GEN collaborators. Eligible studies reported data for children aged 0-60 months with RSV as primary infection with acute lower respiratory infection in community settings, or acute lower respiratory infection necessitating hospital admission; reported data for at least 12 consecutive months, except for in-hospital case fatality ratio (CFR) or for where RSV seasonality is well-defined; and reported incidence rate, hospital admission rate, RSV positive proportion in acute lower respiratory infection hospital admission, or in-hospital CFR. Studies were excluded if case definition was not clearly defined or not consistently applied, RSV infection was not laboratory confirmed or based on serology alone, or if the report included fewer than 50 cases of acute lower respiratory infection. We applied a generalised linear mixed-effects model (GLMM) to estimate RSV-associated acute lower respiratory infection incidence, hospital admission, and in-hospital mortality both globally and regionally (by country development status and by World Bank Income Classification) in 2019. We estimated country-level RSV-associated acute lower respiratory infection incidence through a risk-factor based model. We developed new models (through GLMM) that incorporated the latest RSV community mortality data for estimating overall RSV mortality. This review was registered in PROSPERO (CRD42021252400). FINDINGS: In addition to 317 studies included in our previous review, we identified and included 113 new eligible studies and unpublished data from 51 studies, for a total of 481 studies. We estimated that globally in 2019, there were 33·0 million RSV-associated acute lower respiratory infection episodes (uncertainty range [UR] 25·4-44·6 million), 3·6 million RSV-associated acute lower respiratory infection hospital admissions (2·9-4·6 million), 26 300 RSV-associated acute lower respiratory infection in-hospital deaths (15 100-49 100), and 101 400 RSV-attributable overall deaths (84 500-125 200) in children aged 0-60 months. In infants aged 0-6 months, we estimated that there were 6·6 million RSV-associated acute lower respiratory infection episodes (4·6-9·7 million), 1·4 million RSV-associated acute lower respiratory infection hospital admissions (1·0-2·0 million), 13 300 RSV-associated acute lower respiratory infection in-hospital deaths (6800-28 100), and 45 700 RSV-attributable overall deaths (38 400-55 900). 2·0% of deaths in children aged 0-60 months (UR 1·6-2·4) and 3·6% of deaths in children aged 28 days to 6 months (3·0-4·4) were attributable to RSV. More than 95% of RSV-associated acute lower respiratory infection episodes and more than 97% of RSV-attributable deaths across all age bands were in low-income and middle-income countries (LMICs). INTERPRETATION: RSV contributes substantially to morbidity and mortality burden globally in children aged 0-60 months, especially during the first 6 months of life and in LMICs. We highlight the striking overall mortality burden of RSV disease worldwide, with one in every 50 deaths in children aged 0-60 months and one in every 28 deaths in children aged 28 days to 6 months attributable to RSV. For every RSV-associated acute lower respiratory infection in-hospital death, we estimate approximately three more deaths attributable to RSV in the community. RSV passive immunisation programmes targeting protection during the first 6 months of life could have a substantial effect on reducing RSV disease burden, although more data are needed to understand the implications of the potential age-shifts in peak RSV burden to older age when these are implemented. FUNDING: EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe (RESCEU).

Diagnostic utility and validation of a newly developed real time loop mediated isothermal amplification method for the detection of SARS CoV-2 infection.

Background: Detecting SARS-CoV-2 using a simple real time molecular assay will be helpful for the mitigation efforts in low / middle income countries during the pandemic. We have developed and validated a rapid and simple real time loop mediated isothermal amplification assay (LAMP) for screening of SARS-CoV-2 infection in known infected and non-infected individuals. Methods: Six sets of primers were designed targeting the N-gene of the SARS-CoV-2 (Accession ID MN994468). LAMP reactions were performed using Warm Start 2X Master Mix and real-time PCR machine at 65 °C for 60 cycles with 15 s for each cycle. Results were read by visualizing turbidity under ultraviolet light and real time fluorescence detection through FAM channel of the real time PCR machine. We tested a total of 320 including 240 SARS CoV-2 positive (Ct values <40) and 80 SARS CoV-2 negative samples as tested by a real time RT-PCR using the newly developed LAMP assay. Results: A total of 206 out of 240 SARS CoV-2 positive samples were tested positive by the newly developed LAMP assay with a sensitivity of 86%. All 80 SARS CoV-2 negative samples were tested negative by the newly developed LAMP assay with a specificity of 100%. Conclusion: The newly developed real time LAMP assay has a sensitivity of 86% and specificity of 100% compared to the real time RT-PCR for the detection of SARS CoV-2. The new assay will be useful to screen large number of samples if adopted to minimize the time and cost.

Circulating dengue virus serotypes and vertical transmission in Aedes larvae during outbreak and inter-outbreak seasons in a high dengue risk area of Sri Lanka.

BACKGROUND: Spatial and temporal changes in the dengue incidence are associated with multiple factors, such as climate, immunity among a population against dengue viruses (DENV), circulating DENV serotypes and vertical transmission (VT) of DENV in an area at a given time. The level of VT in a specific location has epidemiological implications in terms of viral maintenance in vectors. Identification of the circulating DENV serotypes in both patients and Aedes mosquito larvae in an area may be useful for the early detection of outbreaks. We report here the results of a prospective descriptive study that was conducted to detect the levels of VT in Aedes mosquito larvae and circulating DENV serotypes in patients and Aedes mosquito larvae from December 2015 to March 2017 in an area of Sri Lanka at high risk for dengue. METHODS: A total of 200 patients with clinically suspected dengue who had been admitted to a tertiary care hospital during a dengue outbreak (3 study periods: December 2015-January 2016, June-August 2016, December 2016-January 2017) and in the inter-outbreak periods (February-May 2016 and September-November 2016) were investigated. Blood samples were drawn from the study participants to test for DENV. The houses of the study participants were visited within 7 days of admission to the hospital, and Aedes larvae were also collected within a radius of 400 m from the houses. The larvae were separately identified to species and then pooled according to each patient's identification number. Patients' sera and the Aedes larvae were tested to identify the infecting DENV serotypes using a reverse transcription PCR (RT-PCR) method. Levels of VT in Aedes mosquito larvae were also identified. RESULTS: All four DENV serotypes (DENV-1 to -4) were identified in the study area. In the early part of the study (December 2015-February 2016), DENV-3 was predominant and from April 2016 to March 2017, DENV-2 became the most predominant type. Four cases of DENV co-infections were noted during the study period in patients. Interestingly, all four DENV serotypes were detected in Aedes albopictus larvae, which was the prominent immature vectorial form identified throughout the study period in the area, showing 9.8% VT of DENV. With the exception of DENV-4, the other three DENV serotypes were identified in Aedes aegypti larvae with a VT of 8.1%. CONCLUSION: Comparatively high rates of VT of DENV was detected in Ae. albopictus and Ae. aegypti larvae. A shift in the predominant DENV serotype with simultaneous circulation of all four DENV serotypes was identified in the study area from December 2015 to March 2017.

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.

Protective immunity against hepatitis B virus infection in a group of vaccinated Sri Lankan military service men following a complete course of vaccination.

Vaccination is the appropriate measure to protect military personnel against the hepatitis B virus (HBV) infection. Testing the military personnel for anti-HBs levels after vaccination is vital in re-vaccinating those that have not developed protective immunity. The aim of the current study was to determine the immunity in a group of vaccinated Sri Lankan military personnel (n = 150; age = 26-44 years) following a complete course of hepatitis B virus surface antigen (HBsAg) vaccination by assessing the antibodies against HBsAg (anti-HBs) levels. Three months after the last dose of the vaccination, blood samples were collected from the study population and tested for anti-HBs levels using a commercially available ELISA. Of the 150 military service men tested, 139 (92.67%) had anti-HBs levels higher than 10 mIU/mL, WHO approved levels for protective immunity against HBV infection. Of the 139 that had sufficient anti-HBs levels, 24% (36/150) had anti-HBs levels between 10 and 100 mIU/mL and 68.67% (103/150) had anti-HBs levels > 100 mIU/mL. Overall, 7.33% (11/150) participants had anti-HBs levels < 10 mIU/mL. Sero-conversion to > 10 mIU/mL anti-HBs was more than 90% in those that were less than 40 years of age and it was less than 90% in those that were more than 40 years of age.

A mini outbreak of human metapneumovirus infection with severe acute respiratory symptoms in a selected group of children presented to a teaching hospital in Sri Lanka.

Human metapneumovirus (hMPV) of the family Paramyxoviridae is a relatively new virus causing severe acute respiratory tract infections (SARI) in children. Data on hMPV infection in Asia including Sri Lanka is limited. We aimed to detect respiratory viruses including hMPV in a selected group of children affected by a small outbreak of SARI presented to the Teaching Hospital, Peradeniya (THP), Sri Lanka in 2014. Nasopharyngeal aspirates (NPA) were obtained from 21 children with SARI and tested for hMPV, influenza A and B, parainfluenza 1, 2 and 3 (PIV 1-3), adenovirus and respiratory syncytial virus (RSV) antigens using an immunofluorescence assay (IFA). In addition, a one step RT-PCR was done for the detection of hMPV from the viral RNA extracts. Of the 21 NPA samples tested for respiratory viral antigens by IFA, two were positive for RSV (9.5%), one was positive for influenza A (4.8%) and one was positive for both adenovirus and PIV-2 (4.8%). Of the 21 NPA viral RNA extracts tested by RT-PCR, 18 (86%) were positive for hMPV, in which 2 were co-infected with RSV and influenza A virus, respectively. hMPV was the predominant cause of SARI outbreak (2014) in children presented to the THP, Sri Lanka.

The Impact of RSV-Associated Respiratory Disease on Children in Asia.

Acute respiratory tract infections (ARTIs) are leading contributors to the global infectious disease burden, which is estimated to be 112,900,000 disability adjusted life years. Viruses contribute to the etiology of ARTIs in a big way compared with other microorganisms. Since the discovery of respiratory syncytial virus (RSV) 61 years ago, the virus has been recognized as a major cause of ARTI and hospitalization in children. The morbidity and mortality attributable to RSV infection appear to be higher in infants < 3 months and in those with known risk factors such as prematurity, chronic lung, and congenital heart diseases. Crowded living conditions, exposure to tobacco smoke, and industrial or other types of air pollution also increase the risk of RSV-associated ARTI. Many epidemiological studies have been conducted in developed countries to understand the seasonal patterns and risk factors associated with RSV infections. Dearth of information on RSV-associated morbidity and mortality in Asian and developing countries indicates the need for regional reviews to evaluate RSV-associated disease burden in these countries. Epidemiological studies including surveillance is the key to track the disease burden including risk factors, seasonality, morbidity, and mortality associated with RSV infection in these countries. These data will contribute to improve the clinical diagnosis and plan preventive strategies in resource-limited developing countries.

Epidemiology and factors influencing varicella infections in tropical countries including Sri Lanka.

Varicella zoster virus (VZV) infections occur worldwide but the epidemiology differs between different geographical regions. Epidemiology of varicella is partly understood in tropical and subtropical regions. Various hypotheses showing differences in exposure rates in different age groups have been proposed. Exposure to VZV during late childhood or adolescent stage causes high morbidity, especially in high school children, university students and young work force in tropical nations. Exposure to VZV infection or sero-prevalence rates through anti-VZV immunoglobulin G appears to be lower in Sri Lanka, similar to other tropical countries prior to the millennium. In contrast, a more recent study in a group of antenatal women showed a relatively higher exposure rate to VZV when compared to the exposure rates prior to 2004 in Sri Lanka. Climatic factors, socioeconomic conditions, mobility and cultural practices appear to play a role in the differences in the exposure rates to VZV infection in the tropics. In most tropical Asian countries including Sri Lanka, routine vaccination against varicella is not carried out. Individuals with negative history for varicella take the vaccine when there is a necessity. Medical and nursing students take the vaccine prior to their clinical training to avoid adulthood varicella.

Comparison of a rapid immuno-chromatography assay with a standard ELISA for the detection of IgM and IgG antibodies against dengue viruses.

A total of 765 blood samples collected from dengue suspected patients admitted to a Teaching Hospital in Sri Lanka were used to compare a rapid ICT assay with a standard ELISA for the detection of anti-dengue virus (DENV) IgM and IgG. Detection accuracy indices including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), Chi square and Cohen's kappa values were determined for the ICT assay using the ELISA as a comparator for the detection of anti-DENV IgM and IgG. The rapid ICT assay showed a sensitivity of 64%, specificity of 75%, NPV of 68% and PPV of 72% for anti-DENV IgM detection. However, all the accuracy indices were relatively higher for the anti-DENV IgG detection by the ICT assay than those for anti-DENV IgM detection. Despite the low sensitivity for anti-DENV IgM detection by the ICT assay, considering the limitations in using ELISAs in resource limited regions, rapid ICT assays would be useful for the detection of more recent DENV infections. As many patients present after fever days 5 in the study area, anti-DENV IgM/IgG would be the suitable marker to be detected by rapid ICT assays in such areas.

Blood group AB is associated with severe forms of dengue virus infection.

Several viral and host factors are believed to contribute to the development of severe forms of dengue such as dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS) following a dengue virus (DENV) infection. The pathogenesis of DHF/DSS is not fully understood, however, host factors like ABO blood groups have been shown to contribute to the severity of DENV infection. The present study investigated the association of blood groups with severity of DENV infection in the northern region of Sri Lanka. The blood-groups of 405 patients positive for DENV NS1 antigen and anti-DENV IgM/IgG were determined using the standard haemagglutination assay recommended by the national blood bank/s. The occurrence of severe dengue in patients with certain blood groups was significantly different (p < 0.001) to those with other blood groups. Patients with AB blood group had more than 2.5 times higher risk of developing DHF than those with other blood groups. On the other hand, patients with blood group O were significantly under represented for DHF relative to the proportion of this blood group in the general population. Thus dengue patients with blood group O appear to have a low risk of developing DHF than those with other blood groups.