Effectiveness of pertussis vaccination in pregnancy to prevent hospitalisation in infants aged <2 months and effectiveness of both primary vaccination and mother's vaccination in pregnancy in infants aged 2-11 months

BackgroundPERTINENT is an active hospital-based surveillance system for pertussis in infants. In 2019, four of the six participating European countries recommended pertussis vaccination in pregnancy. Among infants aged <2 months, we measured the vaccine effectiveness (VE) in pregnancy; among infants aged 2–11 months, VE of vaccination in pregnancy and of primary vaccination (PV).MethodsFrom December 2015 to 2019, we included all infants aged <1 year presenting with pertussis-like symptoms. Using a test-negative-design, cases were infants testing positive for Bordetella pertussis by PCR or culture. Controls were those testing negative for all Bordetella species. Vaccinated mothers were those who received vaccine in pregnancy. Vaccinated infants were those who received ≥1 dose of PV > 14 days before symptom onset. We excluded infants with unknown maternal or PV status or with mothers vaccinated ≤14 days before delivery. We calculated pooled VE as 100 * (1-odds ratio of vaccination) adjusted for study site, onset date in quarters and infants’ age group.ResultsOf 829 infants presenting with pertussis-like symptoms, 336 (41%) were too young for PV. For the VE in pregnancy analysis, we included 75 cases and 201 controls. Vaccination in pregnancy was recorded for 9 cases (12%) and 92 controls (46%), adjusted VE was between 75% [95%CI: 35–91%] and 88% [95%CI: 57–96%].Of 493 infants eligible for PV, we included 123 cases and 253 controls. Thirty-one cases and 98 controls recorded both PV with ≥ 1 dose and vaccination in pregnancy, adjusted VE was between 74% [95%CI: 33–90] and 95% [95%CI: 69–99]; 27 cases and 53 controls recorded PV only, adjusted VE was between 68% [95%CI: 27–86] and 94% [95%CI: 59–99].ConclusionOur findings suggest that vaccination in pregnancy reduces pertussis incidence in infants too young for PV. In infants aged 2–11 months, PV only and both PV and vaccination in pregnancy provide significant protection against severe pertussis.     

Effectiveness of typhoid conjugate vaccine against culture-confirmed typhoid in a peri-urban setting in Karachi: A case-control study

BackgroundEnteric fever, caused by Salmonella Typhi and S. Paratyphi, is a cause of high morbidity and mortality among children in South Asia. Rising antimicrobial resistance presents an additional challenge. Typhoid Conjugate Vaccines (TCV) are recommended by the World Health Organization for use among people 6 months to 45 years old living in endemic settings. This study aimed to assess the effectiveness of TCV against culture-confirmed S. Typhi in Lyari Town, Karachi, Pakistan. This peri-urban town was one of the worst affected by the outbreak of extensively drug resistant (XDR) typhoid that started in November 2016.MethodsA matched case-control study was conducted following a mass immunization campaign with TCV at three key hospitals in Lyari Town Karachi, Pakistan. Children aged 6 months to 15 years presenting with culture-confirmed S. Typhi were enrolled as cases. For each case, at least 1 age-matched hospital control and two age-matched community controls were enrolled. Adjusted odds ratios with 95% confidence intervals (CIs) were calculated using conditional logistic regression.ResultsOf 82 typhoid fever patients enrolled from August 2019 through December 2019, 8 (9·8%) had received vaccine for typhoid. Of the 164 community controls and 82 hospital controls enrolled, 38 (23·2%) community controls and 27 (32·9%) hospital controls were vaccinated for typhoid. The age and sex-adjusted vaccine effectiveness was found to be 72% (95% CI: 34% − 88%). The consumption of meals prepared outside home more than once per month (adjusted odds ratio: 3·72, 95% CI: 1·55- 8·94; p-value: 0·003) was associated with the development of culture-confirmed typhoid.ConclusionA single dose of TCV is effective against culture confirmed typhoid among children aged 6 months to 15 years old in an XDR typhoid outbreak setting of a peri-urban community in Karachi, Pakistan.     

Enhanced surveillance for adverse events following immunization during the 2019 typhoid conjugate vaccine campaign in Harare,Zimbabwe

BackgroundDuring February 25–March 4, 2019, Zimbabwe’s Ministry of Health and Child Care conducted an emergency campaign using 342,000 doses of typhoid conjugate vaccine (TCV) targeting individuals 6 months–15 years of age in eight high-risk suburbs of Harare and up to 45 years of age in one suburb of Harare. The campaign represented the first use of TCV in Africa outside of clinical trials.MethodsThree methods were used to capture adverse events during the campaign and for 42 days following the last dose administered: (1) active surveillance in two Harare hospitals, (2) national passive surveillance, and (3) a post-campaign coverage survey.ResultsThirty-nine adverse events were identified during active surveillance, including 19 seizure cases (16 were febrile), 16 hypersensitivity cases, 1 thrombocytopenia case, 1 anaphylaxis case, and two cases with two conditions. Only 21 (54%) of 39 patients were hospitalized and 38 recovered without sequelae. Attack rates per 100,000 TCV doses administered were highest for seizures (6.27) and hypersensitivity (5.02). Only 6 adverse events were reported through passive surveillance by facilities other than the two active surveillance hospitals. A total of 177 (10%) of 1,817 vaccinees surveyed reported experiencing an adverse event during the post-campaign coverage survey, of which 25 (14%) sought care.ConclusionsIn line with previous evaluations of TCV, enhanced adverse event monitoring during an emergency campaign supports the safety of TCV. The majority of reported events were minor or resulted in recovery without long-term sequelae. Attack rates for seizures and hypersensitivity were low compared with previous active surveillance studies conducted in Kenya and Burkina Faso. Strengthening adverse event monitoring in Zimbabwe and establishing background rates of conditions of interest in the general population may improve future safety monitoring during new vaccine introductions.     

Field challenges to measles elimination in the Democratic Republic of the Congo

BackgroundDuring a measles epidemic, the Ministry of Public Health (MOH) of the Democratic Republic of the Congo conducted supplementary immunization activities (2016-SIA) from August 28-September 3, 2016 throughout Maniema Province. From October 29-November 4, 2016, Médecins Sans Frontières and the MOH conducted a reactive measles vaccination campaign (2016-RVC) targeting children six months to 14 years old in seven health areas with heavy ongoing transmission despite inclusion in the 2016-SIA, and a post-vaccination survey. We report the measles vaccine coverage (VC) and effectiveness (VE) of the 2016-SIA and VC of the 2016-RVC.MethodsA cross-sectional VC cluster survey stratified by semi-urban/rural health area and age was conducted. A retrospective cohort analysis of measles reported by the parent/guardian allowed calculation of the cumulative measles incidence according to vaccination status after the 2016-SIA for an estimation of crude and adjusted VE.ResultsIn November 2016, 1145 children (6–59 months old) in the semi-urban and 1158 in the rural areas were surveyed. Post-2016-SIA VC (documentation/declaration) was 81.6% (95%CI: 76.5–85.7) in the semi-urban and 91.0% (95%CI: 84.9–94.7) in the rural areas. The reported measles incidence in October among children less than 5 years old was 5.0% for 2016-SIA-vaccinated and 11.2% for 2016-SIA-non-vaccinated in the semi-urban area, and 0.7% for 2016-SIA-vaccinated and 4.0% for 2016-SIA-non-vaccinated in the rural area. Post-2016-SIA VE (adjusted for age, sex) was 53.9% (95%CI: 2.9–78.8) in the semi-urban and 78.7% (95%CI: 0–97.1) in the rural areas. Post 2016-RVC VC (documentation/declaration) was 99.1% (95%CI: 98.2–99.6) in the semi-urban and 98.8% (95%CI: 96.5–99.6) in the rural areas.ConclusionsAlthough our VE estimates could be underestimated due to misclassification of measles status, the VC and VE point estimates of the 2016-SIA in the semi-urban area appear suboptimal, and in combination, could not limit the epidemic. Further research is needed on vaccination strategies adapted to urban contexts.     

Association of infant Rib and Alp1 surface protein N-terminal domain immunoglobulin G and invasive Group B Streptococcal disease in young infants

BackgroundVaccine development for Group B Streptococcus (GBS), a common cause of invasive disease in early-infancy and adverse pregnancy outcomes, include exploring widely-expressed GBS surface proteins as vaccine epitopes. We investigated the association between natural infant serum IgG against the RibN and Alp1N domains and risk of invasive GBS disease caused by isolates expressing these proteins.MethodsWe analyzed maternal and infant serum samples from GBS disease cases and infants born to GBS-colonized women controls. Bayesian modelling was used to calculate the GBS homotypic IgG concentration associated with risk reduction of invasive disease in the infant.ResultsPCR-based typing of 85 GBS invasive isolates showed 46 and 24 possessing the gene for Rib and Alp1, respectively. These were matched to 46 and 36 infant controls whose mothers were colonized with GBS expressing Rib and Alp1, respectively. RibN IgG geometric mean concentrations (GMC) were lower in cases than controls among infants (0.01; 95 %CI: 0.01–0.02 vs 0.04; 95 %CI: 0.03–0.06; p < 0.001), no significant difference was found between maternal RibN IgG GMC in cases compared to controls. Alp1N IgG GMC was also lower in infant cases (0.02; 95 %CI: 0.01–0.03) than controls (0.05; 95 %CI: 0.04–0.07; p < 0.001); albeit not so in mothers. An infant IgG threshold ≥ 0.428 and ≥ 0.112 µg/mL was associated with 90 % risk reduction of invasive GBS disease due to Rib and Alp1 expressing strains, respectively.DiscussionLower serum RibN and Alp1N IgG GMC were evident in infants with invasive GBS disease compared with controls born to women colonized with GBS expressing the homotypic protein. These data support the evaluation of Alp family proteins as potential vaccine candidates against invasive GBS disease.     

Impact and effectiveness of the 10-valent pneumococcal conjugate vaccine on invasive pneumococcal disease among children under 5 years of age in the Netherlands

BackgroundIn 2011, the 7-valent pneumococcal conjugate vaccine (PCV7) was replaced by the 10-valent vaccine (PCV10) in the Netherlands. We report on impact and effectiveness against invasive pneumococcal disease (IPD) in children aged under 5 years by switching from PCV7 to PCV10.MethodWe included IPD cases between 2004 and 2019 in children aged < 5 years reported via the national surveillance system. To assess the impact of the PCV10 vaccination program we compared IPD incidence 6-8 years after PCV10 introduction (2017–2019) to the two years just before the switch to PCV10 (2009–2011). We estimated vaccine effectiveness (VE) using the indirect cohort method, comparing vaccination status (at least two vaccine doses) in IPD-cases caused by PCV10 serotypes (cases) to non-PCV10 IPD cases (controls), in children eligible for PCV10.ResultsThe overall incidence decreased from 8.7 (n = 162) in 2009–2011 to 7.3 per 100.000 (n = 127) in 2017–2019 (Incidence rate ratio (IRR) 0.83, 95%CI: 0.66; 1.05). IPD caused by the additional serotypes included in PCV10 declined by 93% (IRR 0.07, 95%CI: 0.02; 0.23). Incidence of non-PCV10 IPD showed a non-significant increase (IRR 1.25, 95%CI: 0.96; 1.63). Among 231 IPD-cases eligible for PCV10, the overall VE was 91% (95%CI: 67; 97) and did not differ by sex or age at diagnosis. Effectiveness against non-PCV10 serotype 19A IPD was non-significant with an estimate of 28% (95%CI:-179; 81).ConclusionPCV10 is highly effective in protecting against IPD in Dutch children under 5 years with limited serotype replacement after switching from PCV7 to PCV10. We found no evidence for significant cross-protection of PCV10 against 19A serotype IPD.     

Understanding influenza vaccine protection in the community: An assessment of the 2013 influenza season in Victoria,Australia

BackgroundThe influenza virus undergoes frequent antigenic drift, necessitating annual review of the composition of the influenza vaccine. Vaccination is an important strategy for reducing the impact and burden of influenza, and estimating vaccine effectiveness (VE) each year informs surveillance and preventative measures. We aimed to describe the influenza season and to estimate the effectiveness of the influenza vaccine in Victoria, Australia, in 2013.MethodsRoutine laboratory notifications, general practitioner sentinel surveillance (including a medical deputising service) data, and sentinel hospital admission surveillance data for the influenza season (29 April to 27 October 2013) were collated in Victoria, Australia, to describe influenza-like illness or confirmed influenza during the season. General practitioner sentinel surveillance data were used to estimate VE against medically-attended laboratory confirmed influenza. VE was estimated using the case test negative design as 1 − adjusted odds ratio (odds of vaccination in cases compared with controls) × 100%. Cases tested positive for influenza while non-cases (controls) tested negative. Estimates were adjusted for age group, week of onset, time to swabbing and co-morbidities.ResultsThe 2013 influenza season was characterised by relatively low activity with a late peak. Influenza B circulation preceded that of influenza A(H1)pdm09, with very little influenza A(H3) circulation. Adjusted VE for all influenza was 55% (95%CI: −11, 82), for influenza A(H1)pdm09 was 43% (95%CI: −132, 86), and for influenza B was 56% (95%CI: −51, 87) Imputation of missing data raised the influenza VE point estimate to 64% (95%CI: 13, 85).ConclusionsClinicians can continue to promote a positive approach to influenza vaccination, understanding that inactivated influenza vaccines prevent at least 50% of laboratory-confirmed outcomes in hospitals and the community.     

Long-term effectiveness of pentavalent and monovalent rotavirus vaccines against hospitalization in Taiwan children

BackgroundTwo rotavirus vaccines (RV1 and RV5) are available on the private market in Taiwan, not included in national immunization program. Scanty reports evaluated the rotavirus vaccine effectiveness (VE) in Asian countries.MethodsFrom February 2014-July 2017, we conducted a prospective case-control study in ten hospitals in Taiwan. Case-patients included children aged 8–59 months, and hospitalized with laboratory-confirmed rotavirus acute gastroenteritis (AGE). For each case patient, up to four controls, rotavirus-negative AGE or non-AGE illnesses, respectively, were matched by gender, age and enrolled date. Vaccination history was confirmed through vaccination card or hospital record. VE was calculated as (1 − odds ratio of vaccination) × 100%.ResultsTotally 4248 AGE patients and 2242 non-AGE controls were enrolled. A total of 330 case-patients with rotavirus AGE, 1226 rotavirus-negative AGE controls and 1122 non-AGE controls were included for analysis. Unvaccinated rate was 85.15% for rotavirus-positive cases, 42.9% for rotavirus-negative controls, and 34.31% for non-AGE controls. VE of two-dose RV1 was 84.9% (95% confidence interval [CI]:77.7%, 90.1%) for rotavirus-negative AGE and 88.9% (95% CI: 83.4%, 92.8%) for non-AGE controls, while VE of three-dose RV5 was 92.5% (95% CI: 85.1%, 96.7%) and 96.4% (95% CI: 91.9%, 98.6%), respectively. For respective vaccine, VEs were not significantly different in term of rotavirus genotypes. VEs of both vaccines declined <80% in children aged three years by combined controls.ConclusionsBoth vaccines provided excellent and sustained protection against rotavirus AGE hospitalization in children in Taiwan, but the effectiveness declined slightly in children aged three years.     

Field evaluation of typhoid conjugate vaccine in a catch-up campaign among children aged 9 months to 15 years in Sindh,Pakistan

BackgroundTyphoid conjugate vaccine (TCV) has recently been introduced in the expanded program for immunization (EPI) in Pakistan. Before its introduction in routine immunization, a onetime catchup campaign among children 9 months to 15 years old was conducted in November 2019. We performed field evaluation of TCV against culture confirmed Salmonella Typhi (S. Typhi) among 9 months to 15 years old children during the catch up campaign in Karachi and Hyderabad.MethodsA rapid assessment of blood culture confirmed S. Typhi was performed. Age eligible cases of culture confirmed S. Typhi were identified from the laboratory networks of Aga Khan University Hospital Karachi and Hyderabad, Kharadar General Hospital Karachi, and Liaqat University of Medical & Health Sciences (LUMHS) Hyderabad. Information on sociodemographic, typhoid vaccination history and antimicrobial resistance was collected using a structured questionnaire.Patient medical records and lab reports were also reviewed to collect information on diagnosis and antimicrobial susceptibility information. Information about the population vaccination coverage during catch-up campaign was obtained from the provincial EPI office. Field performance of TCV in catchup campaign was measured by calculating the effectiveness using rapid screening method which is less resource-intensive technique of calculating vaccine effectiveness (VE).ResultsOverall, 968 culture confirmed typhoid cases were enrolled. Among them, 82% (793/968) were from Karachi and 18% (175/968) from Hyderabad. The average age of the participants was 5.68 years, and 54% (523/968) were male. 6% (62/968) of the culture confirmed S. Typhi cases were multidrug resistant (MDR), and 61% (586/968) were extensively drug resistant (XDR). The VE using the TCV coverage data provided by EPI was 98%.ConclusionTCV is effective against culture confirmed S. Typhi among children aged 9 months to 15 years in the catch-up campaign setting. While typhoid vaccination can significantly decrease the burden of typhoid disease, improvements in sanitation and hygiene are necessary for the prevention of spread of enteric fever. Longer term follow up will be needed to assess the duration of protection and requirement for booster doses of TCV.     

Estimates of pertussis vaccine effectiveness in United States air force pediatric dependents

BackgroundPertussis vaccination compliance is critical for reduction in the prevalence of disease; however, the current acellular pertussis vaccine may not provide sufficient protection from infection. This study examined acellular pertussis vaccine effectiveness (VE) for Air Force dependents less than 12 years of age.MethodsWe conducted a case-control study among Air Force pediatric dependents from 2011 to 2013, comparing cases with positive pertussis test results to controls who received the same lab tests with a negative result. Our study population was categorized by age group and vaccination status based on the Centers for Disease Control and Prevention recommended pertussis vaccination schedule. VE was calculated with respect to vaccination status and pertussis lab results.ResultsWe compared 27 pertussis laboratory positive cases with 974 pertussis laboratory negative controls, 2 months to <12 years old. Comparing completely vaccinated to non-vaccinated patients, the overall VE was 78.3% (95% confidence interval (CI): 48.6, 90.8; p < 0.001). VE was highest among those 15 months to <6 years old: 97.6% (95% CI: 78.5, 99.7; p < 0.001). Children 6 to <12 years old had the lowest VE: 48.5% (95% CI: −74.0, 84.7; p = 0.28). Comparing partially vaccinated patients to nonvaccinated patients yielded 64.2% (95% CI: −7.2, 88.1; p = 0.06) overall VE.ConclusionsAcellular pertussis vaccination was effective at preventing laboratory confirmed pertussis among our Air Force pediatric dependent population, with highest protection among completely vaccinated, young children. Older children received the lowest amount of protection. Partial vaccination had near significant protection. Our overall calculated pertussis VE corroborates other pertussis VE studies looking at similar age groups.     

Effectiveness of quadrivalent influenza vaccination in the first year of a funded childhood program in Queensland,Australia, 2018

BackgroundFollowing high influenza activity in 2017, the state of Queensland, Australia, funded a quadrivalent inactivated influenza vaccination program for children aged 6 months to <5 years in 2018. We calculated influenza vaccine effectiveness (VE) among children eligible for this program.MethodsA matched case-control study was conducted. Cases were identified using Queensland 2018 influenza notification data among children age-eligible for funded vaccination. Controls were drawn from Australian Immunisation Register records of Queensland resident children age-eligible for funded influenza vaccine. Up to 10 controls per case were matched for location and birthdate. First dose vaccination was valid if received ≥14 days prior to specimen collection; a second dose was valid if received ≥28 days after first dose receipt. VE was calculated for vaccine doses and adherence to national recommendations for two doses in the first season (schedule completeness) and adjusted (VE_adj) for sex and First Nations status.ResultsThere were 1,125 cases and 10,645 matched controls analysed. Overall VE_adj against laboratory-confirmed influenza was 51% (95% confidence interval (CI) 41–60). VE_adj was 60% (95% CI 46–70) for children who received two doses in 2018, and 60% (95% CI 48–69) for children vaccinated appropriately according to schedule completeness. VE increased with age.ConclusionsModerate vaccine effectiveness was observed for children eligible for the funded program in Queensland in 2018, adding to the sparse evidence for influenza vaccine use in Australian children. Adhering to the national first season two dose schedule for influenza vaccine receipt in children ensures maximum protection.     

Effectiveness of four doses of pertussis vaccine during infancy diminished in elementary school age: A test-negative case-control study in Japan

ObjectiveThe Japanese national immunization program recommends that children receive 4 doses of acellular pertussis vaccine between 3 months and 2 years of age. Nevertheless, the number of pertussis cases is increasing in elementary school children aged 6–12 years. Therefore, a test-negative case-control study was conducted to assess the effectiveness of the pertussis vaccine program.MethodsSubjects included children aged ≥3 months who visited a collaborating hospital due to pertussis-specific cough between October 2017 and November 2019. All subjects underwent diagnostic tests for pertussis, and those diagnosed as positive were regarded as cases. Subjects diagnosed as pertussis-negative were classified as controls. Vaccination history was collected using a questionnaire administered to parents with reference to immunization records. Logistic regression models were employed to calculate the odds ratio (OR) and 95% confidence interval for laboratory-confirmed pertussis.ResultsOf 187 recruited subjects (120 cases and 67 controls), questionnaire responses were obtained for 145 subjects (95 cases and 50 controls). Compared with unvaccinated subjects, the vaccine effectiveness (VE) of 4 doses was 70% among all subjects and reached to 90% with marginal significance among subjects under 6 years of age. However, among school-aged subjects, the VE was not suggestive of protection against pertussis (VE: 8%). For vaccinees given 4 doses, the OR for developing pertussis increased significantly with longer duration since the fourth dose (compared with <4.5 years, OR of 6.0–8.2 years = 5.74; OR of ≥8.3 years = 3.88; P for trend by duration < 0.01).ConclusionEffectiveness of administering 4 doses of pertussis vaccine during infancy decreases with time passed since the fourth dose. This regimen does not protect school-aged children against pertussis.     

水痘疫苗在学校水痘暴发疫情中保护效果的病例对照研究

目的 评价接种1剂水痘疫苗在学校水痘暴发疫情中的保护效果(vaccine effectiveness, VE)。方法 采用1:2配对病例对照研究,收集中山市2013—2021年水痘暴发疫情调查资料,将病例数≥5例的班的所有病例（共942例）作为病例组,按1:2的比例选取同班、同年龄（±1岁）、同性别的1 884名健康儿童作为对照组,调查其水痘疫苗接种史,采用条件logistic回归分析水痘疫苗保护效果。结果 共调查3～14岁儿童2 826名,儿童接种1剂水痘疫苗的保护效果为58%（95%CI:50%～66%）,3～5岁、6～14岁儿童接种1剂水痘疫苗保护效果分别为75%（95%CI:62%～83%）和51%（95%CI:40%～61%）。儿童接种1剂后≤2年、3～5年、6～8年、≥9年的保护效果分别为78%（95%CI:66%～86%）、66%（95%CI:57%～74%）、51%（95%CI:36%～62%）、23%（95%CI:-11%～46%）。儿童接种1剂水痘疫苗的保护效果随接种后时间的延长而降低（趋势χ²=13.071,P<0.001）。结论 儿童接种1剂水痘疫苗有助于防控水痘暴发疫情,但其保护效果随接种后时间的延长而降低,难以阻断水痘传播。建议儿童及时接种2剂水痘疫苗,以预防学校水痘暴发疫情。     

Effectiveness of the 10-valent pneumococcal conjugate vaccine against radiographic pneumonia among children in rural Bangladesh: A case-control study

BackgroundPneumococcal conjugate vaccine (PCV) effectiveness against radiographic pneumonia in South Asia is unknown. Bangladesh introduced PCV10 in 2015 using a three dose primary series (3 + 0). We sought to measure PCV10 effectiveness for two or more vaccine doses on radiographic pneumonia among vaccine-eligible children in rural Bangladesh.MethodsWe conducted a matched case-control study over two years from 2015 to 2017 using clinic and community controls in three subdistricts of Sylhet, Bangladesh. Cases were vaccine eligible 3–35 month olds at Upazila Health Complex outpatient clinics with World Health Organization-defined radiographic primary endpoint pneumonia (radiographic pneumonia). Clinic controls were matched to cases within a one week time window by age, sex, and clinic and had an illness unlikely to be Streptococcus pneumoniae; community controls were healthy and similarly matched within a one week time window by age and sex, and distance from the clinic. We estimated adjusted vaccine effectiveness (aVE) using conditional logistic regression.ResultsWe matched 1262 cases with 2707 clinic and 2461 community controls. Overall, aVE using clinic controls was 21.4% (95% confidence interval, −0.2%, 38.4%) for ≥2 PCV10 doses and among 3–11 month olds was 47.3% (10.5%, 69.0%) for three doses. aVE increased with higher numbers of doses in clinic control sets (p = 0.007). In contrast, aVE using community controls was 7.6% (95% confidence interval, −22.2%, 30.0%) for ≥2 doses. We found vaccine introduction in the study area faster and less variable than expected with 75% coverage on average, which reduced power. Information bias may also have affected community controls.ConclusionsClinic control analyses show PCV10 prevented radiographic pneumonia in Bangladesh, especially among younger children receiving three doses. While both analyses were underpowered, community control enrollment – compared to clinic controls – was more difficult in a complex, pluralistic healthcare system. Future studies in comparable settings may consider alternative study designs.     

Comparison of test-negative and syndrome-negative controls in SARS-CoV-2 vaccine effectiveness evaluations for preventing COVID-19 hospitalizations in the United States

BackgroundTest-negative design (TND) studies have produced validated estimates of vaccine effectiveness (VE) for influenza vaccine studies. However, syndrome-negative controls have been proposed for differentiating bias and true estimates in VE evaluations for COVID-19. To understand the use of alternative control groups, we compared characteristics and VE estimates of syndrome-negative and test-negative VE controls.MethodsAdults hospitalized at 21 medical centers in 18 states March 11–August 31, 2021 were eligible for analysis. Case patients had symptomatic acute respiratory infection (ARI) and tested positive for SARS-CoV-2. Control groups were test-negative patients with ARI but negative SARS-CoV-2 testing, and syndrome-negative controls were without ARI and negative SARS-CoV-2 testing. Chi square and Wilcoxon rank sum tests were used to detect differences in baseline characteristics. VE against COVID-19 hospitalization was calculated using logistic regression comparing adjusted odds of prior mRNA vaccination between cases hospitalized with COVID-19 and each control group.Results5811 adults (2726 cases, 1696 test-negative controls, and 1389 syndrome-negative controls) were included. Control groups differed across characteristics including age, race/ethnicity, employment, previous hospitalizations, medical conditions, and immunosuppression. However, control-group-specific VE estimates were very similar. Among immunocompetent patients aged 18–64 years, VE was 93 % (95 % CI: 90–94) using syndrome-negative controls and 91 % (95 % CI: 88–93) using test-negative controls.ConclusionsDespite demographic and clinical differences between control groups, the use of either control group produced similar VE estimates across age groups and immunosuppression status. These findings support the use of test-negative controls and increase confidence in COVID-19 VE estimates produced by test-negative design studies.     

Influenza vaccine effectiveness against laboratory-confirmed influenza in a vaccine-mismatched influenza B-dominant season

BackgroundThe 2017–2018 influenza season in Israel was characterized by the predominance of influenza B Yamagata, with a lesser circulation of influenza A(H1N1)pdm09 and influenza A(H3N2). We estimated vaccine effectiveness (VE) of the inactivated influenza vaccine which was selected for use that season.MethodsEnd-of-season VE and 95% confidence intervals (CI) against laboratory-confirmed influenza-like illness (ILI) were estimated by means of the test-negative design. Age-specific VE analysis was carried out using a moving age interval.ResultsSpecimen were obtained from 1,453 community ILI patients; 610 (42.0%) were influenza-positive, among which 69.7% were B, 17.2% A(H1N1)pdm09 and 13.4% A(H3N2). A 98.6% of molecularly characterized influenza B belonged to the Yamagata lineage. Of the sampled individuals, 1320 were suitable for VE analysis. Of those vaccinated, 90.6% received the inactivated trivalent influenza vaccine (TIV) containing a Victoria lineage influenza B-like virus. VE against influenza A differed by age, with the highest VE of 72.9% (95%CI 31.9–89.2%) observed in children 0.5–14 years old, while all ages VE was 46.6% (95%CI 10.4–68.2%). All ages VE against influenza B was 23.2% (95%CI −10.1–46.4%) with age-specific analysis showing non-significant VE estimates. Utilizing a moving age interval of 15 years, afforded a detailed age-specific insight into influenza VE against the influenza viruses circulating during the 2017–2018 season.ConclusionsThe moderate-high 2017–2018 influenza A VE among children and adolescents, supports seasonal influenza vaccination at a young age. The low VE against influenza B in Israel, is most likely the result of influenza B/TIV-mismatch.     

Effects of acute exercise on drug craving in adults with poly-substance use disorder. A randomized controlled trial

ObjectivesTo examine the short-term effects of exercise on drug craving in poly-drug-dependent inpatients, duration of effects, differences between exercise types, explore the relationship between craving and mood, and possible moderators.DesignMulticenter randomized control trial (RCT) with a crossover design.Methods38 (25 completed) inpatients (37.3 ± 6.4 years; 84 % male) from three treatment centers participated in soccer, circuit training and control condition in random order for 45-min. Craving was assessed with a self-rated visual analog scale (VAS), mood with Feeling scale (FS), immediately before and after each condition and 1, 2, and 4 h post interventions. Ratings of perceived exertion (RPE) and heart rate were assessed. Intervention effects were assessed using linear mixed effects model, including moderator analyses.ResultsExercise sessions were perceived as “somewhat hard” to “hard”. Compared to control, there was an immediate reduction in craving after soccer and circuit training (β = −1.35, 95 %CI: 1.96, −0.75, p = 0.000; β = -1.44, 95 %CI: 2.06, −0.83, p = 0.000) that persisted for 4 h (β = −1.11, 95 %CI: 1.72, −0.49, p = 0.000; β = -0.85, 95 %CI: 1.49, −0.22, p = 0.008). Elevations in mood after soccer (β = 1.08, 95 %CI: 0.41, 1.76, p = 0.002) and circuit training (β = 0.99, 95 %CI: 0.32, 1.67, p = 0.004) were significantly larger than control. Depressive disorder and primary drug of use might moderate the effect.ConclusionReduced drug cravings and elevated mood following soccer and circuit training were observed in people with poly-SUDs. Single exercise sessions can be an effective strategy to alleviate craving and potentially prevent relapse and treatment drop-out.     

Acceptance of pneumococcal vaccination in older adults: A general population-based survey

BackgroundPneumococcal infection is a leading cause of disability and death globally. The Hong Kong Government has launched two programmes for pneumococcal vaccination - The Vaccination Subsidy Scheme (VSS) and the Government Vaccination Programme (GVP). This study aimed to examine the enabling factors, obstacles and perception of pneumococcal vaccination, and their association with its uptake in a general Chinese population.MethodsWe performed a population-based, telephone survey in the general public aged 65 or above via simple random sampling. A validated survey based on the Health Belief Model (HBM) was used. Their socio-demographic information; history of previous participation in the GVP or VSS; and self-perceived health status were captured. Binary logistic regression models were constructed to examine the factors independently associated with vaccination.ResultsA total of 1,000 respondents were enrolled in the study, with 402 (40.2%) respondents having intention to join the GVP/VSS in 12 months. Respondents with long-term medical consultant and medication (adjusted odds ratios [aOR] = 1.541, 95% confidence interval (CI): 1.008–2.356, p = 0.046); high levels of perceived susceptibility of infections (aOR = 3.624, 95 %CI: 2.318–5.665, p < 0.001); high levels of perceived benefits of vaccine (aOR = 1.699, 95 %CI: 1.153–2.504, p < 0.001); recommendations from government (aOR = 8.025, 95 %CI: 4.771–13.497, p < 0.001) or physicians (aOR = 7.399, 95 %CI: 3.472–15.764, p = 0.008); and high levels of self-efficacy (aOR = 3.045, 95 %CI: 1.458–6.362, p = 0.003) were more likely to have intention to participate in the vaccination programme.ConclusionsThe acceptance rate of pneumococcal vaccination programme remained suboptimal in the population. The government and physicians should be involved in the promotion of pneumococcal vaccination and GVP/VSS by increasing perceived benefits and self-efficacy, and reducing barriers towards vaccination among the target population. More studies are required to confirm our findings in other settings.     

Influenza vaccine effectiveness to prevent influenza-related hospitalizations and serious outcomes in Canadian adults over the 2011/12 through 2013/14 influenza seasons: A pooled analysis from the Canadian Immunization Research Network (CIRN) Serious Outcomes Surveillance (SOS Network)

BackgroundOngoing assessment of influenza vaccine effectiveness (VE) is critical to inform public health policy. This study aimed to determine the VE of trivalent influenza vaccine (TIV) for preventing influenza-related hospitalizations and other serious outcomes over three consecutive influenza seasons.MethodsThe Serious Outcomes Surveillance (SOS) Network of the Canadian Immunization Research Network (CIRN) conducted active surveillance for influenza in adults ≥16 years (y) of age during the 2011/2012, 2012/2013 and 2013/2014 seasons in hospitals across Canada. A test-negative design was employed: cases were polymerase chain reaction (PCR)-positive for influenza; controls were PCR-negative for influenza and were matched to cases by date, admission site, and age (≥65 y or <65 y). All cases and controls had demographic and clinical characteristics (including influenza immunization status) obtained from the medical record. VE was estimated as 1-OR (odds ratio) in vaccinated vs. unvaccinated patients × 100%. The primary outcome was VE of TIV for preventing laboratory-confirmed influenza-related hospitalization; secondary outcomes included VE of TIV for preventing influenza-related intensive care unit (ICU) admission/mechanical ventilation, and influenza-related death.ResultsOverall, 3394 cases and 4560 controls were enrolled; 2078 (61.2%) cases and 2939 (64.5%) controls were ≥65 y. Overall matched, adjusted VE was 41.7% (95% Confidence Interval (CI): 34.4–48.3%); corresponding VE in adults ≥65 y was 39.3% (95% CI: 29.4–47.8%) and 48.0% (95% CI: 37.5–56.7%) in adults <65 y, respectively. VE for preventing influenza-related ICU admission/mechanical ventilation in all ages was 54.1% (95% CI: 39.8–65.0%); in adults ≥65 y, VE for preventing influenza-related death was 74.5% (95% CI: 44.0–88.4%).ConclusionsWhile effectiveness of TIV to prevent serious outcomes varies year to year, we demonstrate a statistically significant and clinically important TIV VE for preventing hospitalization and other serious outcomes over three seasons. Public health messaging should highlight the overall benefit of influenza vaccines over time while acknowledging year to year variability.ClinicalTrials.gov Identifier: NCT01517191.     

Vaccine effectiveness of PCV13 in a 3 + 1 vaccination schedule

ObjectiveTo assess the vaccine effectiveness (VE) of PCV13 for invasive pneumococcal disease (IPD) regarding the extra six serotypes with a 3 + 1 schedule in Germany.MethodsActive surveillance for IPD in children <16 years eligible for PCV13 vaccination. We used the Broome method and logistic regression to estimate VE.ResultsData on 164/304 reported IPD cases were informative and met the inclusion criteria. VE for the extra six serotypes was 88% [95% confidence interval (CI): 73; 95] and 83% [56; 94] for at least one and for at least two doses respectively. VE for the complete 3 + 1 vaccination schedule was not conclusive because of a wide 95% CI. For serotype 3 VE appeared to be zero with an even wider 95% CI.ConclusionPCV13 VE against the extra six serotypes with the 3 + 1 schedule in Germany was only marginally higher compared to previously published data for the 2 + 1 schedule.