Monitoring Vaccine Effectiveness Research Articles

Estimating vaccine effectiveness against COVID-19 using cause-specific sick leave as an indicator: a nationwide population-based cohort study, Norway, July 2021 – December 2022

BackgroundDue to changes in testing policy and increased use of rapid tests, other indicators for SARS-CoV-2 infections are needed to monitor vaccine effectiveness (VE). We aimed to estimate VE against COVID-19 sick leave (> 3 days, certified by a medical professional) among employed individuals (25–64-years-old) in Norway.MethodsWe performed a nationwide cohort study by collating data from the Emergency preparedness register for COVID-19. We used adjusted Cox proportional hazard models with vaccine status as a time-varying covariate and presented results as adjusted hazard ratios (aHRs) with corresponding 95% confidence intervals. Separate models were run against sick leave and against SARS-CoV-2 infections during the Delta period (June-December 2021), and against sick leave during the Omicron period (January-December 2022) when SARS-CoV-2 PCR-testing was replaced by rapid self-tests and infections were underreported.ResultsWe included 2,236,419 individuals during the Delta period, of whom 73,776 (3.3%) had a reported infection and 54,334 (2.4%) were registered with sick leave. Of the 2,206,952 included individuals in the Omicron period, 300,140 (13.6%) were registered with sick leave. During the Delta period, 55% (26,611) of individuals who had registered sick leave also had a positive test, compared to 32% (96,445) during the Omicron period. The VE against sick leave during the Delta period followed a similar waning pattern to that against SARS-CoV-2 infections. After the second and third dose, the lowest aHRs were estimated for 2–7 days after vaccination for both sick leave (0.25; 95%CI 0.24–0.26 and 0.26; 95% CI 0.24–0.29) and infection ( 0.16; 95% CI 0.15–0.17 and 0.18; 95% CI 0.16–0.19) respectively. During the Omicron period, aHRs for sick leave were higher than during the Delta period, but the lowest aHRs were still found in 2–7 weeks after receiving the second (0.61; 95% CI 0.59–0.64) or third dose (0.63; 95% CI 0.62–0.64).ConclusionOur results showed that sick leave could be a relevant indicator for VE in the surveillance of COVID-19 and a finding that may be important in the surveillance of other respiratory infection.

The relative effectiveness of three and four doses of COVID-19 vaccine in Victoria, Australia: A data linkage study

BackgroundThe Coronavirus Disease 2019 (COVID-19) pandemic led to extensive vaccination campaigns worldwide, including in Australia. Immunity waning and the emergence of new viral variants pose challenges to the effectiveness of vaccines. Our study aimed to assess the relative effectiveness (rVE) of 3 and 4 compared with 2 doses of COVID-19 vaccine. The study focuses on the Victorian population, a majority of whom had no prior exposure to the virus before vaccination. MethodsWe used routinely collected data for the state of Victoria, Australia, to assess rVE during an Omicron-dominant period, 1 June 2022 to 1 March 2023. Immunisation, notifications, hospitalisations and mortality data for residents aged 65 years and older were linked for analysis. Cox proportional hazard regression was used to estimate the rVE against COVID-19 hospitalisation or death, accounting for key confounders with vaccination as a time-varying covariate. ResultsIn 1,070,113 people 65 years or older who had received their second dose, a third and fourth dose of a COVID-19 vaccine significantly reduced the hazard of hospitalisation or death compared to two doses. rVE was highest within two weeks from administration at 40 % (95 % CI: 0 % to 64 %) and 66 % (95 % CI: 60 % to 71 %) for a third and fourth dose, respectively. Additional protection conferred by third and fourth doses waned over time from administration. ConclusionsOur findings underscore the need for additional vaccine doses and updated vaccine strategies. These findings have implications for public health advice and COVID-19 vaccine strategies. Further research and monitoring of vaccine effectiveness in real-world settings are warranted to inform ongoing pandemic response efforts.

Monitoring COVID-19 vaccine effectiveness against COVID-19 hospitalisation and death using electronic health registries in ≥65 years old population in six European countries, October 2021 to November 2022.

Within the ECDC-VEBIS project, we prospectively monitored vaccine effectiveness (VE) against COVID-19 hospitalisation and COVID-19-related death using electronic health registries (EHR), between October 2021 and November 2022, in community-dwelling residents aged 65-79 and ≥80 years in six European countries. EHR linkage was used to construct population cohorts in Belgium, Denmark, Luxembourg, Navarre (Spain), Norway and Portugal. Using a common protocol, for each outcome, VE was estimated monthly over 8-week follow-up periods, allowing 1 month-lag for data consolidation. Cox proportional-hazards models were used to estimate adjusted hazard ratios (aHR) and VE = (1- aHR) × 100%. Site-specific estimates were pooled using random-effects meta-analysis. For ≥80 years, considering unvaccinated as the reference, VE against COVID-19 hospitalisation decreased from 66.9% (95% CI: 60.1; 72.6) to 36.1% (95% CI: -27.3; 67.9) for the primary vaccination and from 95.6% (95% CI: 88.0; 98.4) to 67.7% (95% CI: 45.9; 80.8) for the first booster. Similar trends were observed for 65-79 years. The second booster VE against hospitalisation ranged between 82.0% (95% CI: 75.9; 87.0) and 83.9% (95% CI: 77.7; 88.4) for the ≥80 years and between 39.3% (95% CI: -3.9; 64.5) and 80.6% (95% CI: 67.2; 88.5) for 65-79 years. The first booster VE against COVID-19-related death declined over time for both age groups, while the second booster VE against death remained above 80% for the ≥80 years. Successive vaccine boosters played a relevant role in maintaining protection against COVID-19 hospitalisation and death, in the context of decreasing VE over time. Multicountry data from EHR facilitate robust near-real-time VE monitoring in the EU/EEA and support public health decision-making.

Clinical Performance of Cobas 6800 for the Detection of High-Risk Human Papillomavirus in Urine Samples.

Testing for high-risk human papillomavirus (HPV) as part of primary cervical cancer screening has become more common recently. The Cobas 6800, an FDA-approved cervical screening platform, detects 14 high-risk HPVs, including HPV16 and HPV18. However, this test is limited to only women, which leads to low screening rates in trans men and other non-binary people. The cervical screening of trans men and other genders, especially those lying on the female-to-male spectrum, is equally important. Furthermore, cisgender males, particularly homosexuals, are also prone to chronic HPV infections and serve as HPV carriers, transmitting it to women and other men through sexual contact. Another limitation of the test is its invasive specimen collection, which induces discomfort and genital dysphoria. Therefore, there is a need for an innovative, less invasive method that would allow the sampling process to be more comfortable. In this study, we assess the performance of the Cobas 6800 for high-risk HPV detection in urine samples spiked with HPV16, HPV18, and HPV68. The limit of detection (LOD) was calculated using a dilution series (1.25-10,000 copies/mL) over a course of three days. Furthermore, the clinical validation was performed by calculating sensitivity, specificity, and accuracy. The limit of detection ranged from 50-1000 copies/mL depending upon the genotype. Moreover, the urine test demonstrated a high clinical sensitivity of 93%, 94%, and 90% for HPV16, HPV18, and HPV68, with 100% specificity. The overall percent agreement was calculated to be 95% for both HPV16 and HPV18, and 93% for HPV68. The high concordance, reproducibility, and clinical performance of the current assay suggest that the urine-based HPV test fulfills the requirements for its use in primary cervical screening. Moreover, it has the potential to be used for mass screening to not only identify high-risk individuals, but also to monitor vaccine effectiveness.

Simultaneous Quantitative SARS-CoV-2 Antigen and Host Antibody Detection and Pre-Screening Strategy at the Point of Care.

As COVID-19 pandemic public health measures are easing globally, the emergence of new SARS-CoV-2 strains continue to present high risk for vulnerable populations. The antibody-mediated protection acquired from vaccination and/or infection is seen to wane over time and the immunocompromised populations can no longer expect benefit from monoclonal antibody prophylaxis. Hence, there is a need to monitor new variants and its effect on vaccine performance. In this context, surveillance of new SARS-CoV-2 infections and serology testing are gaining consensus for use as screening methods, especially for at-risk groups. Here, we described an improved COVID-19 screening strategy, comprising predictive algorithms and concurrent, rapid, accurate, and quantitative SARS-CoV-2 antigen and host antibody testing strategy, at point of care (POC). We conducted a retrospective analysis of 2553 pre- and asymptomatic patients who were tested for SARS-CoV-2 by RT-PCR. The pre-screening model had an AUC (CI) of 0.76 (0.73-0.78). Despite being the default method for screening, body temperature had lower AUC (0.52 [0.49-0.55]) compared to case incidence rate (0.65 [0.62-0.68]). POC assays for SARS-CoV-2 nucleocapsid protein (NP) and spike (S) receptor binding domain (RBD) IgG antibody showed promising preliminary results, demonstrating a convenient, rapid (<20 min), quantitative, and sensitive (ng/mL) antigen/antibody assay. This integrated pre-screening model and simultaneous antigen/antibody approach may significantly improve accuracy of COVID-19 infection and host immunity screening, helping address unmet needs for monitoring vaccine effectiveness and severe disease surveillance.

Canine Parvovirus in Turkey: First Whole-Genome Sequences, Strain Distribution, and Prevalence.

Canine parvovirus (CPV) is a significant pathogenic virus with up to 100% morbidity and 91% mortality rates, especially in unvaccinated puppies. The emergence of new strains, interspecies transmission, and vaccine effectiveness can be enabled by just a few base changes in the CPV genome. Therefore, to cope with CPV disease, it is important to identify the viral agent and regularly monitor vaccine effectiveness against new strains. The present study has investigated CPV's genetic profile in Turkey by collecting 80 samples from dogs in Turkey between 2020 and 2022. These samples and all sequences previously studied for CPV in Turkey were analyzed for whole-genome sequences, nationwide strain distribution over the two years, and the central Turkey prevalence rate. Next-generation sequencing was used for the genome study, Sanger sequencing for strain detection, and PCR for the prevalence analyses. The CPV-2 variants circulating in Turkey form their own cluster while being closely related to Egypt variants. Substantial amino acid changes were detected in antigenically important regions of the VP2 gene. Moreover, CPV-2b has become the most frequent genotype in this region, while the incidence of CPV-2c is predicted to increase gradually over the coming years. The prevalence of CPV in central Turkey was 86.27%. This study thus provides powerful insights to further our understanding of CPV's genetic profile in Turkey and suggests that up-to-date vaccination efficacy studies are urgently needed.

Detection of SARS-CoV-2 infections in passengers arriving from China and their implications on air travel and public health in Italy

Detection of SARS-CoV-2 infections in passengers arriving from China and their implications on air travel and public health in Italy

Estimating vaccine effectiveness against SARS-CoV-2 infection, hospitalization and death from ecologic data in Costa Rica

BackgroundClinical trials and individual-level observational data in Israel demonstrated approximately 95% effectiveness of mRNA-based vaccines against symptomatic SARS-CoV-2 infection. Individual-level data are not available in many countries, particularly low- and middle- income countries. Using a novel Poisson regression model, we analyzed ecologic data in Costa Rica to estimate vaccine effectiveness and assess the usefulness of this approach.MethodsWe used national data from December 1, 2020 to May 13, 2021 to ascertain incidence, hospitalizations and deaths within ecologic units defined by 14 age groups, gender, 105 geographic areas, and day of the epidemic. Within each unit we used the proportions of the population with one and with two vaccinations, primarily tozinameran. Using a non-standard Poisson regression model that included an ecologic-unit-specific rate factor to describe rates without vaccination and a factor that depended on vaccine effectiveness parameters and proportions vaccinated, we estimated vaccine effectiveness.ResultsIn 3.621 million persons aged 20 or older, there were 125,031 incident cases, 7716 hospitalizations, and 1929 deaths following SARS-CoV-2 diagnosis; 73% of those aged ≥ 75 years received two doses. For one dose, estimated effectiveness was 59% (95% confidence interval 53% to 64%) for SARS-CoV-2 incidence, 76% (68% to 85%) for hospitalizations, and 63% (47% to 80%) for deaths. For two doses, the respective estimates of effectiveness were 93% (90% to 96%), 100% (97% to 100%), and 100% (97% to 100%).ConclusionsThese effectiveness estimates agree well with findings from clinical trials and individual-level observational studies and indicate high effectiveness in the general population of Costa Rica. This novel statistical approach is promising for countries where ecologic, but not individual-level, data are available. The method could also be adapted to monitor vaccine effectiveness over calendar time.

Rapidly adapting primary care sentinel surveillance across seven countries in Europe for COVID-19 in the first half of 2020: strengths, challenges, and lessons learned.

As the COVID-19 pandemic began in early 2020, primary care influenza sentinel surveillance networks within the Influenza - Monitoring Vaccine Effectiveness in Europe (I-MOVE) consortium rapidly adapted to COVID-19 surveillance. This study maps system adaptations and lessons learned about aligning influenza and COVID-19 surveillance following ECDC / WHO/Europe recommendations and preparing for other diseases possibly emerging in the future. Using a qualitative approach, we describe the adaptations of seven sentinel sites in five European Union countries and the United Kingdom during the first pandemic phase (March–September 2020). Adaptations to sentinel systems were substantial (2/7 sites), moderate (2/7) or minor (3/7 sites). Most adaptations encompassed patient referral and sample collection pathways, laboratory testing and data collection. Strengths included established networks of primary care providers, highly qualified testing laboratories and stakeholder commitments. One challenge was the decreasing number of samples due to altered patient pathways. Lessons learned included flexibility establishing new routines and new laboratory testing. To enable simultaneous sentinel surveillance of influenza and COVID-19, experiences of the sentinel sites and testing infrastructure should be considered. The contradicting aims of rapid case finding and contact tracing, which are needed for control during a pandemic and regular surveillance, should be carefully balanced.

Molecular probes of spike ectodomain and its subdomains for SARS-CoV-2 variants, Alpha through Omicron.

Since the outbreak of the COVID-19 pandemic, widespread infections have allowed SARS-CoV-2 to evolve in human, leading to the emergence of multiple circulating variants. Some of these variants show increased resistance to vaccine-elicited immunity, convalescent plasma, or monoclonal antibodies. In particular, mutations in the SARS-CoV-2 spike have drawn attention. To facilitate the isolation of neutralizing antibodies and the monitoring of vaccine effectiveness against these variants, we designed and produced biotin-labeled molecular probes of variant SARS-CoV-2 spikes and their subdomains, using a structure-based construct design that incorporated an N-terminal purification tag, a specific amino acid sequence for protease cleavage, the variant spike-based region of interest, and a C-terminal sequence targeted by biotin ligase. These probes could be produced by a single step using in-process biotinylation and purification. We characterized the physical properties and antigenicity of these probes, comprising the N-terminal domain (NTD), the receptor-binding domain (RBD), the RBD and subdomain 1 (RBD-SD1), and the prefusion-stabilized spike ectodomain (S2P) with sequences from SARS-CoV-2 variants of concern or of interest, including variants Alpha, Beta, Gamma, Epsilon, Iota, Kappa, Delta, Lambda, Mu, and Omicron. We functionally validated probes by using yeast expressing a panel of nine SARS-CoV-2 spike-binding antibodies and confirmed sorting capabilities of variant probes using yeast displaying libraries of plasma antibodies from COVID-19 convalescent donors. We deposited these constructs to Addgene to enable their dissemination. Overall, this study describes a matrix of SARS-CoV-2 variant molecular probes that allow for assessment of immune responses, identification of serum antibody specificity, and isolation and characterization of neutralizing antibodies.

Comprehensive narrative review of real-world COVID-19 vaccines: viewpoints and opportunities.

Currently, people all over the world have been affected by coronavirus disease 2019 (COVID-19). Fighting against COVID-19 is the top priority for all the countries and nations. The development of a safe and effective COVID-19 vaccine is considered the optimal way of ending the pandemic. Three hundred and 44 vaccines were in development, with 149 undergoing clinical research and 35 authorized for emergency use as to March 15 of 2022. Many studies have shown the effective role of COVID-19 vaccines in preventing SARS-CoV-2 infections as well as serious and fatal COVID-19 cases. However, tough challenges have arisen regarding COVID-19 vaccines, including long-term immunity, emerging COVID-19 variants, and vaccine inequalities. A systematic review was performed of recent COVID-19 vaccine studies, with a focus on vaccine type, efficacy and effectiveness, and protection against SARS-CoV-2 variants, breakthrough infections, safety, deployment and vaccine strategies used in the real-world. Ultimately, there is a need to establish a unified evaluation standard of vaccine effectiveness, monitor vaccine safety and effectiveness, along with the virological characteristics of SARS-CoV-2 variants; and determine the most useful booster schedule. These aspects must be coordinated to ensure timely responses to beneficial or detrimental situations. In the future, global efforts should be directed toward effective and immediate vaccine allocations, improving vaccine coverage, SARS-CoV-2 new variants tracking, and vaccine booster development.

Validation of a quantitative lateral flow immunoassay (LFIA)-based point-of-care (POC) rapid test for SARS-CoV-2 neutralizing antibodies

With the widespread use of coronavirus disease 2019 (COVID-19) vaccines, a rapid and reliable method to detect SARS-CoV-2 neutralizing antibodies (NAbs) is extremely important for monitoring vaccine effectiveness and immunity in the population. The purpose of this study was to evaluate the performance of the RapiRead™ reader and the TestNOW™ COVID-19 NAb rapid point-of-care (POC) test for quantitative measurement of antibodies against the spike protein receptor-binding domain of severe respiratory syndrome coronavirus 2 (SARS-CoV-2) in different biological matrices compared to chemiluminescence immunoassay (CLIA) methods. Ninety-four samples were collected and analyzed using a RapiRead™ reader and TestNOW™ COVID-19 NAb kits for detecting neutralizing antibodies, and then using two CLIAs. The data were compared statistically using the Kruskal-Wallis test for more than two groups or the Mann-Whitney test for two groups. Specificity and sensitivity were evaluated using a receiver operating characteristic (ROC) curve. Good correlation was observed between the rapid lateral flow immunoassay (LFIA) test system and both CLIA methods. RapiRead™ reader/TestNOW™ COVID-19 NAb vs. Maglumi: correlation coefficient (r) = 0.728 for all patients; r = 0.841 for vaccinated patients. RapiRead™ reader/TestNOW™ COVID-19 NAb vs. Mindray: r = 0.6394 in all patients; r = 0.8724 in vaccinated patients. The time stability of the POC serological test was also assessed considering two times of reading, 12 and 14 minutes. The data revealed no significant differences. The use of a RapiRead™ reader and TestNOW™ COVID-19 NAb assay is a quantitative, rapid, and valid method for detecting SARS-CoV-2 neutralizing antibodies and could be a useful tool for screening studies of SARS-CoV-2 infection and assessing the efficacy of vaccines in a non-laboratory context.

Prioritise research on vaccines for pregnant and breastfeeding women

Prioritise research on vaccines for pregnant and breastfeeding women

EP333: Tracking the emergence of SARS-CoV-2 variants of concern in vaccinated and unvaccinated patients

Emerging infectious organisms, such as SARS-CoV-2, create public health crises that demand real-time tracking and ongoing surveillance of new variants to monitor changes in transmissibility, virulence, and effectiveness of vaccines. Aegis Sciences BioPharma Laboratory has sequenced over 250,000 RT-PCR-confirmed SARS-CoV-2 positive specimens from patients across the United States and Puerto Rico and evaluated the emergence, community spread, and dominance of variants of concern (VOC) in vaccinated and unvaccinated individuals. Through a collaboration with Walgreens, Aegis Sciences BioPharma Laboratory performs COVID-19 testing on patient specimens from all over the United States. Patients schedule appointments via an online portal, submit health data and vaccination status for physician review, and perform socially-distanced, self-collections from the Walgreens pharmacy drive-through while being observed by a trained clinical team member. SARS-CoV-2 positive specimens with an average cycle threshold (Ct) value of <30 were selected for sequencing based on their state’s testing volume and overall population statistics. SARS-CoV-2 genome sequencing and lineage analysis was performed via an optimized workflow using the Illumina COVIDSeq RUO Kits with the NovaSeq 6000 sequencer and the Illumina DRAGEN COVID Lineage Application. The prevalence and spread of variants of concern was evaluated in both vaccinated and unvaccinated patients. Since March 2021, Aegis has submitted over 250,000 sequences from COVID-19 positive patient specimens to the GISAID database, including 437 unique SARS-CoV-2 lineages. Starting in May, the patient’s vaccination status was captured to help monitor vaccine effectiveness and compare variant spread in vaccinated versus unvaccinated individuals. In total, 170,019 patient specimens with a vaccination status have been sequenced. From March to May 2021, Alpha (B.1.1.7) cases increased from 8% to 66%. At Alpha’s peak (May to Mid-June), the average rate of breakthrough cases neared 10% of total sequenced samples. In early June, Delta (B.617.2) cases accounted for only 3% of samples but quickly rose to 60% while Alpha declined from 38% to 6%. From July to November 2021, Delta and its sub-lineages (AY) have dominated and accounted for >90% of all cases with an average breakthrough rate of ∼30% overall. In early August, Delta’s AY sublineages emerged and have since become more prevalent than their B.617.2 parent lineage. Of note, AY.25 (33.54%), AY.44 (37.69%), and AY.39 (36.79%) also have increased vaccine breakthrough rates with the highest breakthrough rate in AY.103 (41.36%). Monitoring viral variant trends and epidemiology through community surveillance programs is critical during a public health crisis. The data generated through these collaborations is vital to tracking viral evolution and understanding changes in transmissibility, virulence, and vaccine effectiveness. Aegis’ sequencing and analysis of >250,000 SARS CoV-2 specimens will continue to contribute to our understanding of COVID-19 for years to come.

COVID-19 vaccine is correlated with favourable epidemiological indicators in the Auvergne-Rhône-Alpes region (France): An ecological study

COVID-19 vaccination has proven to be effective in preventing severe cases, reducing viral load, and transmissibility. The aim of this study was to evaluate the impact of vaccination 11 months after implementation on epidemiological indicators and the effective reproduction number in one French region. We plotted four indicators with vaccination coverage as the explaining variable and estimated the impact of vaccination using the reduction rates in infections and hospital admissions. A reduction of 98% in COVID-19-related hospitalisation 11 months after the vaccine campaign began in January 2021 has been reported while vaccine coverage increased over time. Those results do not make it possible to postulate a causal relationship but do support the effect of vaccination against multiple variants of concern. Non-pharmaceutical measures remain necessary to attain complete epidemic control. Open epidemiological data should be considered to monitor vaccine effectiveness wherever possible.

Invalid measles vaccine dose administration and vaccine effectiveness in Ethiopia.

IntroductionEthiopia endorsed the African regional measles elimination goal in 2012 and has been implementing measles elimination strategies. Administration of measles vaccine before the age of nine months decreases seroconversion. Ensuring administration of valid doses and monitoring vaccine effectiveness is crucial for achieving measles elimination. The objective of the study was to describe the magnitude of invalid measles dose administration and vaccine effectiveness in Ethiopia.Methodswe analysed the 2016 Ethiopian Demographic and Health Survey (EDHS) immunization coverage data for Ethiopia to determine the age at measles vaccine administration and proportion of measles age invalid doses administered. The national measles surveillance data for children with birthdates that match 12-23 months old children surveyed in the EDHS 2016, were analysed to determine the Proportion of Cases Vaccinated (PCV) with one dose of measles vaccine. We estimated the effectiveness of measles vaccine by using the proportion of measles cases vaccinated (PCV) from measles surveillance data and the measles vaccination coverage among children aged 12-23 months reported in the demographic health survey (DHS) done in 2016 (Percent of Population Vaccinated for measles, PPV). The screening method was used to estimate measles vaccine effectiveness at national level and for regions which reported more than 30 measles cases among children 9-23 months of age in the 2013-2015 period. The correlation between the median age of invalid doses administered, proportion of invalid doses and measles vaccine effectiveness was analysed.Resultsat national level, the proportion of invalid measles dose administration was 27.6% for children aged 12-35 months surveyed in the 2016 DHS survey in Ethiopia. Among children reported in the measles case-based surveillance database with birthdates that match the children surveyed in the Ethiopian DHS 2016, the proportion of measles cases vaccinated with a single dose of measles vaccine in the 2013-2015 period was 22.7%. The vaccine effectiveness for single dose measles vaccination was estimated at 75.3%. The measles vaccine effectiveness was low for regions with high proportion of invalid dose administration and lower median age of invalid dose administration. The median age of measles dose administered before the age of nine months was significantly correlated with measles vaccine effectiveness (r=0.971, p=0.001) in the respective regions.Conclusionthe proportion of invalid measles dose administration is very high in Ethiopia and is associated with lower vaccine effectiveness. Further assessment should be carried out to understand the underlying root causes for invalid dose administration, focusing on areas with high proportion of invalid measles doses. The national program should devise strategies to promote timely vaccination as per the national schedule, and to revaccinate those vaccinated before 9 months of age. The ministry of health should also strengthen the platform for immunization in the 2nd year life, to ensure high routine immunization coverage with two doses of measles vaccine to achieve the measles elimination goal in Ethiopia.

Rubella IgM epidemiology in the pre-rubella vaccination era in Uganda

BackgroundControl of Rubella and Congenital Rubella Syndrome using vaccination has shown great success in the America’s. Uganda is due to introduce the Rubella vaccine however the magnitude of transmission is not well documented. Therefore this study was done to determine IgM sero-prevalance for Rubella in order to help monitor vaccine effectiveness post introduction of the vaccine in routine vaccination programme.MethodsA retrospective review of suspected measles cases data for the reporting period January 2007 to December 2016 in Uganda was Done. rubella IgM testing was done on 15,296 of the cases and the data was analyzed using STATA version 13.ResultsIn total 15,296 cases were tested and 4255 (27.8%) tested positive and among females aged 15-49 years 88 out of 322 (27%) tested positive. The age distribution range was 0–80 years, rubella IgM positivity was reported in all the 15 regions of Uganda and throughout the ten year period in every month. Age group 5–15 years had OR 2.5 p-value < 0.001 of being rubella IgM positive compared to age < 5 years and testing measles IgM negative OR 6.3 p-value < 0.001.ConclusionRubella is endemic in Uganda and although rubella IgM positivity is highest in the age 5-15 years even the younger, older and women of reprodutive age are affected. This means the risk of Congenital Rubella Syndrome is high hence the need to introduce the rubella vaccine for infants and pregnant mothers and continued surveillance to enhance its control.

The Use of Test-negative Controls to Monitor Vaccine Effectiveness: A Systematic Review of Methodology.

The test-negative design is an increasingly popular approach for estimating vaccine effectiveness (VE) due to its efficiency. This review aims to examine published test-negative design studies of VE and to explore similarities and differences in methodological choices for different diseases and vaccines. We conducted a systematic search on PubMed, Web of Science, and Medline, for studies reporting the effectiveness of any vaccines using a test-negative design. We screened titles and abstracts and reviewed full texts to identify relevant articles. We created a standardized form for each included article to extract information on the pathogen of interest, vaccine(s) being evaluated, study setting, clinical case definition, choices of cases and controls, and statistical approaches used to estimate VE. We identified a total of 348 articles, including studies on VE against influenza virus (n = 253), rotavirus (n = 48), pneumococcus (n = 24), and nine other pathogens. Clinical case definitions used to enroll patients were similar by pathogens of interest but the sets of symptoms that defined them varied substantially. Controls could be those testing negative for the pathogen of interest, those testing positive for nonvaccine type of the pathogen of interest, or a subset of those testing positive for alternative pathogens. Most studies controlled for age, calendar time, and comorbidities. Our review highlights similarities and differences in the application of the test-negative design that deserve further examination. If vaccination reduces disease severity in breakthrough infections, particular care must be taken in interpreting vaccine effectiveness estimates from test-negative design studies.

Over-diagnosis of Rotavirus Infection in Infants Due to Detection of Vaccine Virus.

An accurate rotavirus diagnosis is important for clinical management and monitoring active disease and vaccine effectiveness. Between 2016-2018, rotavirus-positive results in our laboratory were from vaccine virus shedding in 71/152 (46.7%) infants with a request for rotavirus testing. Routine infant diagnostic testing should ideally distinguish vaccine from wild-type viruses.

Determining effectiveness of rotavirus vaccine by immunochromatography and reverse transcriptase polymerase chain reaction: A comparison

IntroductionBecause of the large animal reservoirs and reassortment capacity of rotaviruses (RVs) that pose the possibilities of waning the effectiveness of RV-vaccines, it remains essential to monitor vaccine effectiveness (VE) regularly. Although reverse transcription polymerase chain reaction (RT-PCR) remains sensitive for RV detection, physicians, especially in Japan, frequently use immunochromatography (IC)-based kits for RV diagnosis. Recently, IC is being used to calculate VE also. Herein, we investigated the validity of VEs determined by IC compared to that by RT-PCR during an outbreak in Shizuoka Prefecture, Japan. MethodsRVs in the stool or rectal swabs from children with acute gastroenteritis (AGE) were tested first by IC in the clinic and then by RT-PCR in the laboratory. A test-negative study design was used to examine VE. ResultsAlthough the specificity of IC assay revealed 100%, its sensitivity remained weaker (67%) than that of RT-PCR that increased up to 88% depending on disease severity. VE assessed by IC remained stronger than that by RT-PCR: 79% (95% CI: 39–93%) by IC, and 58% (95% CI: −20% to 90%) by RT-PCR. However, VEs by IC and RT-PCR appeared almost similar in higher disease severity: 81.5% (95% CI: 40–94%) by IC and 72% (95% CI: 7–92%) by RT-PCR at severity ≥7, while 97.5% (95% CI: 77–99.7%) by IC and 92% (95% CI: 58–98%) by RT-PCR at severity ≥11. We showed that RV-vaccinated children had 80% [OR = 0.192 (95% CI: 0.052–0.709) less chance to be detected by IC. ConclusionAlthough the sensitivity and specificity of IC differ by brand type, generally, IC is not as sensitive as RT-PCR. Despite the VEs remain higher by IC, it looks comparable with that of RT-PCR in severe cases implying that VEs evaluated by IC against severe illness remain useful for VE-monitoring.