Serious adverse event following immunization and thromboembolic events associated with COVID19 vaccination: An analysis of nationwide causality assessment from India

BackgroundVaccines against the COVID-19 pandemic were introduced in late 2020. The present study has been conducted to study the serious Adverse Events Following Immunization (AEFIs) reported for COVID-19 vaccines from India.MethodsSecondary data analysis of the causality assessment reports for the 1112 serious AEFIs published by the Ministry of Health & Family Welfare, Government of India, was conducted. For the current analysis, all the reports published till 29.03.2022 were included. The primary outcome variables analyzed were the consistent causal association and the thromboembolic events.ResultsThe majority of the serious AEFIs assessed were either coincidental (578, 52%) or vaccine product related (218, 19.6%). All the serious AEFIs were reported among the Covishield (992, 89.2%) and COVAXIN (120, 10.8%) vaccines. Among these, 401 (36.1%) were deaths, and 711 (63.9%) were hospitalized and recovered. On adjusted analysis, females, the younger age group and non-fatal AEFIs showed a statistically significant consistent causal association with COVID-19 vaccination. Thromboembolic events were reported among 209 (18.8%) of the analyzed participants, with a significant association with higher age and case fatality rate.ConclusionDeaths reported under serious AEFIs were found to have a relatively lower consistent causal relationship with the COVID-19 vaccines than the recovered hospitalizations in India. No consistent causal association was found between the thromboembolic events and the type of COVID-19 vaccine administered in India.     

Anemia and Related Factors in Preschool Children in the Southern Rural Lao People's Democratic Republic

Anemia is a severe public health problem in the Lao People's Democratic Republic (PDR). Consequently, a new control strategy to reduce the burden of anemia has been introduced for preschool children (aged 6-52 months). The objective of this study was to assess the current prevalence of anemia and related factors in preschool children in southern rural Lao PDR. A population-based cross-sectional study was carried out in six communities in Songkhone district, Savannakheth province, in February 2009. As a result, the prevalence of anemia was found to be 48.9% (95% confidence interval (CI), 43.5-54.3), although most cases were mild. A multiple logistic regression analysis indicated that there was no protective effect of breastfeeding against anemia. The anemia prevalence was higher in 1) children aged 6-23 months (Odds Ratio (OR) = 1.73, 95% CI, 1.02-2.90) than in older children, 2) children in large families (6 or more members) (OR = 1.96, 95% CI, 1.17-3.29), and 3) children in three remote villages with relatively difficult access to markets (OR = 3.01, 95% CI, 1.25-7.47).In Lao PDR, improvement of food practices and home-fortified food supplementation interventions are essential. High-risk groups should be targeted and a long-term health education program that aims to modify food habits implemented. Furthermore, in settings where iron deficiency is not the only cause of anemia, combining an iron supplement with other measures is necessary.     

The challenges of detecting Taenia solium and neurocysticercosis in low and middle-income countries: A scoping review of Lao People's Democratic Republic

Objective

Taenia solium is a tapeworm of global importance due to the burden of disease associated with human epilepsy caused by neurocysticercosis. Unfortunately, diagnostic challenges impede control efforts in many low and middle-income countries. This review examines publications concerning Taenia species in the Lao PDR with a focus on T. solium to inform future research and control programmes.

Methods

PubMed and Scopus databases were primary sources of evidence. Publications must have reported taeniasis or T. solium results from Lao PDR. Publications repeating results or samples were combined into unique projects.

Results

A total of 64 publications were included and summarised into 46 projects. The majority of projects applied faecal microscopy as their only diagnostic technique. As a result, the specific species of Taenia was often not determined. Only five projects used molecular techniques to identify the species observed. Only case report of neurocysticercosis has been published. The northern region was included in half the number of projects compared to the south, despite being a high-risk area T. solium.

Conclusions

The diagnostic challenge of determining the species of Taenia present in a faecal sample presents a significant limitation to the control of T. solium in Lao PDR and is an experience that is relevant to many other low and middle-income countries. There must be an improved understanding of the distribution and frequency of T. solium if disease control efforts are to be intensified to reduce the burden of neurocysticercosis, as encouraged by WHO and others. It is hoped that this can be achieved through non-biological risk mapping tools and the more frequent application of molecular tools to routine sample collection. Diagnostic tools that are applicable to low resource settings should be a priority area of research for T. solium.     

An integrated, multistudy analysis of the safety of Ann Arbor strain live attenuated influenza vaccine in children aged 2-17 years

Please cite this paper as: Ambrose et al. (2011) An integrated, multistudy analysis of the safety of Ann Arbor strain live attenuated influenza vaccine in children aged 2–17 years. Influenza and Other Respiratory Viruses 5(6), 389–397. Background Trivalent, Ann Arbor strain, live attenuated influenza vaccine (LAIV) is approved in several countries for use in eligible children aged ≥2 years. Objective To describe the safety of Ann Arbor strain LAIV in children aged 2–17 years. Methods An integrated analysis of randomized, controlled trials of LAIV. Results A total of 4245 and 10 693 children received ≥1 dose of LAIV in year 1 of 6 trivalent inactivated influenza vaccine (TIV)‐controlled and 14 placebo‐controlled studies, respectively; 3212 children were revaccinated in year 2 of 4 placebo‐controlled studies. Compared with placebo for days 0–10 post‐vaccination, LAIV recipients exhibited increased runny/stuffy nose (+7%), headache (+7%), and tiredness/decreased activity (+2%) after dose 1; and a higher rate of decreased appetite (+4%) after year 2 revaccination. Compared with TIV, only runny/stuffy nose was increased (dose 1, +12%; dose 2, +4%). Compared with initial vaccination, LAIV reactogenicity was lower after dose 2 in year 1 and revaccination in year 2. Unsolicited adverse events (AEs) increased with LAIV in some comparisons were headache, nasal congestion/rhinorrhea, rhinitis, and pyrexia; ear pain and lower respiratory illness were decreased. There was no evidence of an increase in any potential vaccine‐related serious AE in LAIV recipients. Among children aged 2–17 years and specifically aged 24–35 months, there was no evidence that lower respiratory illness or wheezing illness occurred at a higher rate in LAIV recipients. Conclusion This analysis supports the safety of Ann Arbor strain LAIV in children aged 2–17 years and provides a consensus assessment of events expected after vaccination.     

Exploring the effect of previous inactivated influenza vaccination on seasonal influenza vaccine effectiveness against medically attended influenza: Results of the European I‐MOVE multicentre test‐negative case‐control study, 2011/2012‐2016/2017

Background

Results of previous influenza vaccination effects on current season influenza vaccine effectiveness (VE) are inconsistent.

Objectives

To explore previous influenza vaccination effects on current season VE among population targeted for vaccination.

Methods

We used 2011/2012 to 2016/2017 I‐MOVE primary care multicentre test‐negative data. For each season, we compared current season adjusted VE (aVE) between individuals vaccinated and unvaccinated in previous season. Using unvaccinated in both seasons as a reference, we then compared aVE between vaccinated in both seasons, current only, and previous only.

Results

We included 941, 2645 and 959 influenza‐like illness patients positive for influenza A(H1N1)pdm09, A(H3N2) and B, respectively, and 5532 controls. In 2011/2012, 2014/2015 and 2016/2017, A(H3N2) aVE point estimates among those vaccinated in previous season were ?68%, ?21% and ?19%, respectively; among unvaccinated in previous season, these were 33%, 48% and 46%, respectively (aVE not computable for influenza A(H1N1)pdm09 and B). Compared to current season vaccination only, VE for both seasons' vaccination was (i) similar in two of four seasons for A(H3N2) (absolute difference [ad] 6% and 8%); (ii) lower in three of four seasons for influenza A(H1N1)pdm09 (ad 18%, 26% and 29%), in two seasons for influenza A(H3N2) (ad 27% and 39%) and in two of three seasons for influenza B (ad 26% and 37%); (iii) higher in one season for influenza A(H1N1)pdm09 (ad 20%) and influenza B (ad 24%).

Conclusions

We did not identify any pattern of previous influenza vaccination effect. Prospective cohort studies documenting influenza infections, vaccinations and vaccine types are needed to understand previous influenza vaccinations' effects.

     

The manufacturing process should remain the focus for severe febrile reactions in children administered an Australian inactivated influenza vaccine during 2010

Influenza vaccine safety is an ongoing issue. In 2010, inactivated trivalent influenza vaccines (TIVs), Fluvax^® and Fluvax Junior^® manufactured by CSL Biotherapies (‘CSL’), Parkville, Australia, were associated with a marked increase in febrile seizures (FS) in children <5 years old. Extensive investigations initially failed to identify a root cause. The company's researchers recently published two papers outlining their latest findings. Cytokine responses to TIV were measured in paediatric whole blood assays (WBA); NF‐κB activation was assessed using a HEK293 cell line reporter assay. CSL suggest that the combination of new influenza strains (H1N1 A/California/7/2009 and B/Brisbane/60/2008), increased complexes of viral RNA and lipid in the vaccine, and inherent sensitivities of some children <5 years old caused elevated inflammatory responses resulting in FS. Whilst the papers provide insight into pathogenesis, much remains unclear. The WBA were from only 10 ‘healthy’ children, potentially affecting generalisability of the results and reliability of these in vitro tests in assessing future influenza vaccine safety. Increased fever rates (without FS) found in CSL TIV studies between 2005 and 2010 suggest a long‐standing contribution to reactogenicity from the manufacturing process. More detailed comparisons with non‐CSL vaccines would have helped elucidate the relative contribution of patient/strain factors and the manufacturing process. The focus remains on manufacturing process differences as the key causative factor of elevated febrile responses. Studies underway, of modified vaccines in young children, will determine whether reactogenicity issues have been successfully addressed and whether CSL TIV can be relicensed in children <5 years of age.     

Safety and immunogenicity of an inactivated thimerosal‐free influenza vaccine in infants and children

Objective Few prospective studies of inactivated split virion influenza vaccine have been conducted in infants and children. Our objective was to evaluate the safety, reactogenicity and immunogenicity of a thimerosal‐free inactivated influenza vaccine (Fluvax^®; CSL Limited, Parkville, Australia) in children aged 6 months to <9 years. Methods A prospective, open‐label, phase III clinical trial was conducted in 298 healthy children previously unvaccinated with influenza, commencing in the Southern Hemisphere 2005 autumn. Participants were divided into two groups (Group A: ≥6 months to <3 years; Group B: ≥3 years to <9 years), and received two doses of the 2005 vaccine, and one dose of the 2006 vaccine one year later (Group A: 0·25 ml per dose; Group B: 0·5 ml per dose). Vaccine safety and reactogenicity was evaluated for 30 days after each dose. Immunogenicity was assessed using hemagglutination inhibition and single radial hemolysis assays. Results There were no withdrawals due to adverse events (AEs). The majority of solicited local and systemic AEs were of mild severity. A maximum intensity of severe was reported for injection site pain and fever by only 3·0% and 3·4% of participants, respectively. The vaccine was immunogenic for all antigens, with ≥95% of both younger and older children achieving seroprotection after dose 2. Conclusions This thimerosal‐free inactivated influenza vaccine had a favorable safety profile and was immunogenic in children aged ≥6 months and <9 years. Primary and booster vaccination produced consistently immunogenic responses including in children under 3 years of age receiving 0·25 ml doses of vaccine.     

Repeated stool sampling and use of multiple techniques enhance the sensitivity of helminth diagnosis: A cross-sectional survey in southern Lao People's Democratic Republic

Intestinal parasitic infections are common in Lao People's Democratic Republic (Lao PDR). We investigated the accuracy of the Kato-Katz (KK) technique in relation to varying stool sampling efforts, and determined the effect of the concurrent use of a quantitative formalin-ethyl acetate concentration technique (FECT) for helminth diagnosis and appraisal of concomitant infections. The study was carried out between March and May 2006 in Champasack province, southern Lao PDR. Overall, 485 individuals aged ≥6 months who provided three stool samples were included in the final analysis. All stool samples were subjected to the KK technique. Additionally, one stool sample per individual was processed by FECT. Diagnosis was done under a light microscope by experienced laboratory technicians. Analysis of three stool samples with KK plus a single FECT was considered as diagnostic ‘gold’ standard and resulted in prevalence estimates of hookworm, Opisthorchis viverrini, Ascaris lumbricoides, Trichuris trichiura and Schistosoma mekongi infection of 77.9%, 65.0%, 33.4%, 26.2% and 24.3%, respectively. As expected, a single KK and a single FECT missed a considerable number of infections. While our diagnostic ‘gold’ standard produced similar results than those obtained by a mathematical model for most helminth infections, the ‘true’ prevalence predicted by the model for S. mekongi (28.1%) was somewhat higher than after multiple KK plus a single FECT (24.3%). In the current setting, triplicate KK plus a single FECT diagnosed helminth infections with high sensitivity. Hence, such a diagnostic approach might be utilised for generating high-quality baseline data, assessing anthelminthic drug efficacy and rigorous monitoring of community interventions.     

First human infection of avian influenza A(H5N6) virus reported in Lao People's Democratic Republic,February–March 2021

In March 2021, Lao People''s Democratic Republic (Laos) reported an avian influenza A(H5N6) virus infection in a 5‐year‐old child identified through sentinel surveillance. This was the first human A(H5N6) infection reported outside of China. A multidisciplinary investigation undertook contact tracing and enhanced human and animal surveillance in surrounding villages and live bird markets. Seven Muscovy ducks tested positive for highly pathogenic avian influenza A(H5N6) viruses. Sequenced viruses belonged to clade 2.3.4.4h and were closely related to viruses detected in poultry in Vietnam and to previous viruses detected in Laos. Surveillance and coordinated outbreak response remain essential to global health security.     

Assessment of the benefits of seasonal influenza vaccination: Elements of a framework to interpret estimates of vaccine effectiveness and support robust decision‐making and communication

Systematic reviews and meta‐analyses confirm that influenza vaccination reduces the risk of influenza illness by between about 40% and 60% in seasons when circulating influenza stains are well matched to vaccine strains. Influenza vaccine effectiveness (IVE) estimates, however, are often discordant and a source of confusion for decision makers. IVE assessments are increasingly publicized and are often used by policy makers to make decisions about the value of seasonal influenza vaccination. But there is limited guidance on how IVE should be interpreted or used to inform policy. There are several limitations to the use of IVE for decision‐making: (a) IVE studies have methodological issues that often complicate the interpretation of their value; and (b) the full impact of vaccination will almost always be greater than the impact assessed by a point estimate of IVE in specific populations or settings. Understanding the strengths and weaknesses of study methodologies and the fundamental limitations of IVE estimates is important for the accuracy of interpretations and support of policy makers’ decisions. Here, we review a comprehensive set of issues that need to be considered when interpreting IVE and determining the full benefits of influenza vaccination. We propose that published IVE values should be assessed using an evaluative framework that includes influenza‐specific outcomes, types of VE study design, and confounders, among other factors. Better interpretation of IVE will improve the broader assessment of the value of influenza vaccination and ultimately optimize the public health benefits in seasonal influenza vaccination.     

2015/16 I‐MOVE/I‐MOVE+ multicentre case‐control study in Europe: Moderate vaccine effectiveness estimates against influenza A(H1N1)pdm09 and low estimates against lineage‐mismatched influenza B among children

Background

During the 2015/16 influenza season in Europe, the cocirculating influenza viruses were A(H1N1)pdm09 and B/Victoria, which was antigenically distinct from the B/Yamagata component in the trivalent influenza vaccine.

Methods

We used the test‐negative design in a multicentre case‐control study in twelve European countries to measure 2015/16 influenza vaccine effectiveness (VE) against medically attended influenza‐like illness (ILI) laboratory‐confirmed as influenza. General practitioners swabbed a systematic sample of consulting ILI patients and a random sample of influenza‐positive swabs was sequenced. We calculated adjusted VE against influenza A(H1N1)pdm09, A(H1N1)pdm09 genetic group 6B.1 and influenza B overall and by age group.

Results

We included 11 430 ILI patients, of which 2272 were influenza A(H1N1)pdm09 and 2901 were influenza B cases. Overall VE against influenza A(H1N1)pdm09 was 32.9% (95% CI: 15.5‐46.7). Among those aged 0‐14, 15‐64 and ≥65 years, VE against A(H1N1)pdm09 was 31.9% (95% CI: ? 32.3 to 65.0), 41.4% (95% CI: 20.5‐56.7) and 13.2% (95% CI: ? 38.0 to 45.3), respectively. Overall VE against influenza A(H1N1)pdm09 genetic group 6B.1 was 32.8% (95% CI: ? 4.1 to 56.7). Among those aged 0‐14, 15‐64 and ≥65 years, VE against influenza B was ? 47.6% (95% CI: ? 124.9 to 3.1), 27.3% (95% CI: ? 4.6 to 49.4) and 9.3% (95% CI: ? 44.1 to 42.9), respectively.

Conclusions

Vaccine effectiveness (VE) against influenza A(H1N1)pdm09 and its genetic group 6B.1 was moderate in children and adults, and low among individuals ≥65 years. Vaccine effectiveness (VE) against influenza B was low and heterogeneous among age groups. More information on effects of previous vaccination and previous infection is needed to understand the VE results against influenza B in the context of a mismatched vaccine.

     

Influenza vaccine effectiveness against influenza A subtypes in Europe: Results from the 2021–2022 I‐MOVE primary care multicentre study

BackgroundIn 2021–2022, influenza A viruses dominated in Europe. The I‐MOVE primary care network conducted a multicentre test‐negative study to measure influenza vaccine effectiveness (VE).MethodsPrimary care practitioners collected information on patients presenting with acute respiratory infection. Cases were influenza A(H3N2) or A(H1N1)pdm09 RT‐PCR positive, and controls were influenza virus negative. We calculated VE using logistic regression, adjusting for study site, age, sex, onset date, and presence of chronic conditions.ResultsBetween week 40 2021 and week 20 2022, we included over 11 000 patients of whom 253 and 1595 were positive for influenza A(H1N1)pdm09 and A(H3N2), respectively. Overall VE against influenza A(H1N1)pdm09 was 75% (95% CI: 43–89) and 81% (95% CI: 45–93) among those aged 15–64 years. Overall VE against influenza A(H3N2) was 29% (95% CI: 12–42) and 25% (95% CI: −41 to 61), 33% (95% CI: 14–49), and 26% (95% CI: −22 to 55) among those aged 0–14, 15–64, and over 65 years, respectively. The A(H3N2) VE among the influenza vaccination target group was 20% (95% CI: −6 to 39). All 53 sequenced A(H1N1)pdm09 viruses belonged to clade 6B.1A.5a.1. Among 410 sequenced influenza A(H3N2) viruses, all but eight belonged to clade 3C.2a1b.2a.2.DiscussionDespite antigenic mismatch between vaccine and circulating strains for influenza A(H3N2) and A(H1N1)pdm09, 2021–2022 VE estimates against circulating influenza A(H1N1)pdm09 were the highest within the I‐MOVE network since the 2009 influenza pandemic. VE against A(H3N2) was lower than A(H1N1)pdm09, but at least one in five individuals vaccinated against influenza were protected against presentation to primary care with laboratory‐confirmed influenza.     

Seroepidemiology: an underused tool for designing and monitoring vaccination programmes in low‐ and middle‐income countries

Seroepidemiology, the use of data on the prevalence of bio‐markers of infection or vaccination, is a potentially powerful tool to understand the epidemiology of infection before vaccination and to monitor the effectiveness of vaccination programmes. Global and national burden of disease estimates for hepatitis B and rubella are based almost exclusively on serological data. Seroepidemiology has helped in the design of measles, poliomyelitis and rubella elimination programmes, by informing estimates of the required population immunity thresholds for elimination. It contributes to monitoring of these programmes by identifying population immunity gaps and evaluating the effectiveness of vaccination campaigns. Seroepidemiological data have also helped to identify contributing factors to resurgences of diphtheria, Haemophilus Influenzae type B and pertussis. When there is no confounding by antibodies induced by natural infection (as is the case for tetanus and hepatitis B vaccines), seroprevalence data provide a composite picture of vaccination coverage and effectiveness, although they cannot reliably indicate the number of doses of vaccine received. Despite these potential uses, technological, time and cost constraints have limited the widespread application of this tool in low‐income countries. The use of venous blood samples makes it difficult to obtain high participation rates in surveys, but the performance of assays based on less invasive samples such as dried blood spots or oral fluid has varied greatly. Waning antibody levels after vaccination may mean that seroprevalence underestimates immunity. This, together with variation in assay sensitivity and specificity and the common need to take account of antibody induced by natural infection, means that relatively sophisticated statistical analysis of data is required. Nonetheless, advances in assays on minimally invasive samples may enhance the feasibility of including serology in large survey programmes in low‐income countries. In this paper, we review the potential uses of seroepidemiology to improve vaccination policymaking and programme monitoring and discuss what is needed to broaden the use of this tool in low‐ and middle‐income countries.     

Literature review of the epidemiology of influenza B disease in 15 countries in the Asia‐Pacific region

Influenza control strategies focus on the use of trivalent influenza vaccines containing two influenza A virus subtypes and one of the two circulating influenza type B lineages (Yamagata or Victoria). Mismatches between the vaccine B lineage and the circulating lineage have been regularly documented in many countries, including those in the Asia‐Pacific region. We conducted a literature review with the aim of understanding the relative circulation of influenza B viruses in Asia‐Pacific countries. PubMed and Western Pacific Region Index Medicus were searched for relevant articles on influenza type B published since 1990 in English language for 15 Asia‐Pacific countries. Gray literature was also accessed. From 4834 articles identified, 121 full‐text articles were analyzed. Influenza was reported as an important cause of morbidity in the Asia‐Pacific region, affecting all age groups. In all 15 countries, influenza B was identified and associated with between 0% and 92% of laboratory‐confirmed influenza cases in any one season/year. Influenza type B appeared to cause more illness in children aged between 1 and 10 years than in other age groups. Epidemiological data for the two circulating influenza type B lineages remain limited in several countries in the Asia‐Pacific, although the co‐circulation of both lineages was seen in countries where strain surveillance data were available. Mismatches between circulating B lineages and vaccine strains were observed in all countries with available data. The data suggest that a shift from trivalent to quadrivalent seasonal influenza vaccines could provide additional benefits by providing broader protection.