Serial population-based serosurveys for COVID-19 in two neighbourhoods of Karachi, Pakistan

Objective: To determine population-based estimates of coronavirus disease 2019 (COVID-19) in a densely populated urban community of Karachi, Pakistan. Methods: Three cross-sectional surveys were conducted in April, June and August 2020 in low- and high-transmission neighbourhoods. Participants were selected at random to provide blood for Elecsys immunoassay for detection of anti-severe acute respiratory syndrome coronavirus-2 antibodies. A Bayesian regression model was used to estimate seroprevalence after adjusting for the demographic characteristics of each district. Results: In total, 3005 participants from 623 households were enrolled in this study. In Phase 2, adjusted seroprevalence was estimated as 8.7% [95% confidence interval (CI) 5.1-13.1] and 15.1% (95% CI 9.4-21.7) in low- and high-transmission areas, respectively, compared with 0.2% (95% CI 0-0.7) and 0.4% (95% CI 0-1.3) in Phase 1. In Phase 3, it was 12.8% (95% CI 8.3-17.7) and 21.5% (95% CI 15.6-28) in low- and high-transmission areas, respectively. The conditional risk of infection was 0.31 (95% CI 0.16-0.47) and 0.41 (95% CI 0.28-0.52) in low- and high-transmission neighbourhoods, respectively, in Phase 2. Similar trends were observed in Phase 3. Only 5.4% of participants who tested positive for COVID-19 were symptomatic. The infection fatality rate was 1.66%, 0.37% and 0.26% in Phases 1, 2 and 3, respectively. Conclusion: Continuing rounds of seroprevalence studies will help to improve understanding of secular trends and the extent of infection during the course of the pandemic. &nbsp;</p

Global respiratory syncytial virus-associated mortality in young children (RSV GOLD): a retrospective case series

Background Respiratory syncytial virus (RSV) infection is an important cause of pneumonia mortality in young children. However, clinical data for fatal RSV infection are scarce. We aimed to identify clinical and socioeconomic characteristics of children aged younger than 5 years with RSV-related mortality using individual patient data. Methods In this retrospective case series, we developed an online questionnaire to obtain individual patient data for clinical and socioeconomic characteristics of children aged younger than 5 years who died with community-acquired RSV infection between Jan 1, 1995, and Oct 31, 2015, through leading research groups for child pneumonia identified through a comprehensive literature search and existing research networks. For the literature search, we searched PubMed for articles published up to Feb 3, 2015, using the key terms “RSV”, “respiratory syncytial virus”, or “respiratory syncytial viral” combined with “mortality”, “fatality”, “death”, “died”, “deaths”, or “CFR” for articles published in English. We invited researchers and clinicians identified to participate between Nov 1, 2014, and Oct 31, 2015. We calculated descriptive statistics for all variables. Findings We studied 358 children with RSV-related in-hospital death from 23 countries across the world, with data contributed from 31 research groups. 117 (33%) children were from low-income or lower middle-income countries, 77 (22%) were from upper middle-income countries, and 164 (46%) were from high-income countries. 190 (53%) were male. Data for comorbidities were missing for some children in low-income and middle-income countries. Available data showed that comorbidities were present in at least 33 (28%) children from low-income or lower middle-income countries, 36 (47%) from upper middle-income countries, and 114 (70%) from high-income countries. Median age for RSV-related deaths was 5·0 months (IQR 2·3–11·0) in low-income or lower middle-income countries, 4·0 years (2·0–10·0) in upper middle-income countries, and 7·0 years (3·6–16·8) in high-income countries. Interpretation This study is the first large case series of children who died with community-acquired RSV infection. A substantial proportion of children with RSV-related death had comorbidities. Our results show that perinatal immunisation strategies for children aged younger than 6 months could have a substantial impact on RSV-related child mortality in low-income and middle-income countries

Global respiratory syncytial virus–related infant community deaths

Background Respiratory syncytial virus (RSV) is a leading cause of pediatric death, with >99% of mortality occurring in low- and lower middle-income countries. At least half of RSV-related deaths are estimated to occur in the community, but clinical characteristics of this group of children remain poorly characterized. Methods The RSV Global Online Mortality Database (RSV GOLD), a global registry of under-5 children who have died with RSV-related illness, describes clinical characteristics of children dying of RSV through global data sharing. RSV GOLD acts as a collaborative platform for global deaths, including community mortality studies described in this supplement. We aimed to compare the age distribution of infant deaths <6 months occurring in the community with in-hospital. Results We studied 829 RSV-related deaths <1 year of age from 38 developing countries, including 166 community deaths from 12 countries. There were 629 deaths that occurred <6 months, of which 156 (25%) occurred in the community. Among infants who died before 6 months of age, median age at death in the community (1.5 months; IQR: 0.8−3.3) was lower than in-hospital (2.4 months; IQR: 1.5−4.0; P < .0001). The proportion of neonatal deaths was higher in the community (29%, 46/156) than in-hospital (12%, 57/473, P < 0.0001). Conclusions We observed that children in the community die at a younger age. We expect that maternal vaccination or immunoprophylaxis against RSV will have a larger impact on RSV-related mortality in the community than in-hospital. This case series of RSV-related community deaths, made possible through global data sharing, allowed us to assess the potential impact of future RSV vaccines

Influenza virus surveillance in Pakistan during 2008-2011.

There is little information about influenza among the Pakistani population. In order to assess the trends of Influenza-like-Illness (ILI) and to monitor the predominant circulating strains of influenza viruses, a country-wide lab-based surveillance system for ILI and Severe Acute Respiratory Illness (SARI) with weekly sampling and reporting was established in 2008. This system was necessary for early detection of emerging novel influenza subtypes and timely response for influenza prevention and control.Five sentinel sites at tertiary care hospitals across Pakistan collected epidemiological data and respiratory samples from Influenza-like illness (ILI) and severe acute respiratory illness (SARI) cases from January 2008 to December 2011. Samples were typed and sub-typed by Real-Time RT-PCR assay.A total of 6258 specimens were analyzed; influenza virus was detected in 1489 (24%) samples, including 1066 (72%) Influenza type A and 423 (28%) influenza type B viruses. Amongst influenza A viruses, 25 (2%) were seasonal A/H1N1, 169 (16%) were A/H3N2 and 872 (82 %) were A(H1N1)pdm09. Influenza B virus circulation was detected throughout the year along with few cases of seasonal A/H1N1 virus during late winter and spring. Influenza A/H3N2 virus circulation was mainly observed during summer months (August-October).The findings of this study emphasize the need for continuous and comprehensive influenza surveillance. Prospective data from multiple years is needed to predict seasonal trends for vaccine development and to further fortify pandemic preparedness

Prediction of clinical factors associated with pandemic influenza A (H1N1) 2009 in Pakistan.

BACKGROUND: Influenza is a viral infection that can lead to serious complications and death(s) in vulnerable groups if not diagnosed and managed in a timely manner. This study was conducted to improve the accuracy of predicting influenza through various clinical and statistical models. METHODOLOGY: A retrospective cross sectional analysis was done on demographic and epidemiological data collected from March 2009 to March 2010. Patients were classified as ILI or SARI using WHO case definitions. Respiratory specimens were tested by RT-PCR. Clinical symptoms and co-morbid conditions were analyzed using binary logistic regression models. RESULTS: In the first approach, analysis compared children (≤12) and adults (>12). Of 1,243 cases, 262 (21%) tested positive for A(H1N1)pdm09 and the proportion of children (≤12) and adults (>12) were 27% and 73% respectively. Four symptoms predicted influenza in children: fever (OR 2.849, 95% CI 1.931-8.722), cough (OR 1.99, 95% CI 1.512-3.643), diarrhea (OR 2.100, 95% CI 2.040-3.25) and respiratory disease (OR 3.269, 95% CI 2.128-12.624). In adults, the strongest clinical predictor was fever (OR 2.80, 95% CI 1.025-3.135) followed by cough (OR 1.431, 95% CI 1.032-2.815). In the second instance, patients were separated into two groups: SARI 326 (26%) and ILI 917 (74%) cases. Male to female ratio was 1.41∶1.12 for SARI and 2∶1.5 for ILI cases. Chi-square test showed that fever, cough and sore throat were significant factors for A(H1N1)pdm09 infections (p = 0.008). CONCLUSION: Studies in a primary care setting should be encouraged focused on patients with influenza-like illness to develop sensitive clinical case definition that will help to improve accuracy of detecting influenza infections. Formulation of a standard "one size fits all" case definition that best correlates with influenza infections can help guide decisions for additional diagnostic testing and also discourage unjustified antibiotic prescription and usage in clinical practice

Seasonality of influenza and its association with meteorological parameters in two cities of Pakistan: A time series analysis.

BackgroundInfluenza is known to have a specific pattern of seasonality the reasons for which are yet to be fully ascertained. Temperate zones show influenza epidemic during the winter months. The tropical and subtropical regions show more diverse influenza outbreak patterns. This study explores the seasonality of influenza activity and predicts influenza peak based on historical surveillance time series data in Islamabad and Multan, Pakistan.MethodsThis is a descriptive study of routinely collected monthly influenza sentinel surveillance data and meteorological data from 2012-16 in two sentinel sites of Pakistan: Islamabad (North) and Multan (Central).ResultsMean number of cases of influenza and levels of precipitation were higher in Islamabad compared to Multan. Mean temperature and humidity levels were similar in both the cities. The number of influenza cases rose with decrease in precipitation and temperature in Islamabad during 2012-16, although the same cannot be said about humidity. The relationship between meteorological parameters and influenza incidence was not pronounced in case of Multan. The forecasted values in both the cities showed a significant peak during the month of January.ConclusionThe influenza surveillance system gave a better understanding of the disease trend and could accurately forecast influenza activity in Pakistan

Exploring the relationship between SARS-CoV-2 variants, illness severity at presentation, in-hospital mortality and COVID-19 vaccination in a low middle-income country: A retrospective cross-sectional study

Background and aims: COVID-19 morbidity and mortality varied globally through the pandemic. We studied the relationship of SARS-CoV-2 variants of concern (VOC) with COVID-19 severity and mortality among hospitalized patients in Pakistan.Methods: A retrospective review of clinical, laboratory, and vaccination data of 197 COVID-19 adult patients at the Aga Khan University Hospital, Karachi between April 2021, and February 2022 was performed. SARS-CoV-2 VOC identified in respiratory samples were analyzed. Univariate and multivariate analysis was conducted to identify factors associated with COVID-19 outcomes.Results: The median age of cases was 55 years and 51.8% were males. Twenty-four percent of females were pregnant. Of COVID-19 cases, 48.2% had nonsevere disease, while 52.8% had severe/critical disease. Hypertension (48%) and diabetes mellitus (41%) were common comorbids. SARS-CoV-2 VOC identified comprised; Omicron (55.3%), Beta (14.7%), Alpha (13.7%), Delta (12.7%), and Gamma (3.6%) variants. Most (59.7%) study subjects were unvaccinated. Of vaccines, 88% had received inactivated virus COVID-19 vaccines. Increased risk of severe disease was associated with age ≥50 years (odds ratio [OR]: 5.73; 95% confidence interval [CI]: [2.45-13.7]), as well as with diabetes mellitus (OR: 4.24; 95% CI: [1.82-9.85]). Full vaccination (OR: 0.25; 95% CI: [0.11-0.58]) or infection with Omicron (OR: 0.42; 95% CI: [0.23-0.74]) was associated with reduced disease severity. The risk of mortality increased with age ≥50 years (OR: 5.07; 95% CI: [1.92-13.42]) and a history of myocardial infarction (OR: 5.11; 95% CI: [1.45-17.93]) whilst, infection with Omicron was found to reduce the risk (OR: 0.22; 95% CI: [0.10-0.53]).Conclusion: Our study describes the relationship between the severity of COVID-19, in-hospital mortality in relation to SARS-CoV-2 variants, and the impact of COVID-19 vaccination in Pakistan. Outcomes were more favorable in younger individuals, after vaccinations and with Omicron variant infections. Most cases received inactivated virus vaccines therefore these data highlight the protection provided against severe COVID-19

Phylogenetic tree of the second variable region of RSV group A & B genotypes and subtypes.

<p>The prototype strain A2 and 18537 were used as the out groups in the analysis. These trees were constructed using the neighbor-joining algorithm with 1,000 bootstrap replicates using MEGA 5. The genotypes are indicated by the brackets on the right side. Only bootstrap values over 50% are displayed at the branch nodes.</p

Weekly and Monthly Distribution of RSV-positive cases from Dec 2011-March 2012.

<p>Weekly and Monthly Distribution of RSV-positive cases from Dec 2011-March 2012.</p