Pre-vaccine Era Research Articles

Prevalence of High-Risk Human Papillomavirus in Cervical Intraepithelial Neoplasia in the Pre-Vaccine Era - China, 2017-2018.

Human papillomavirus (HPV) type-specific strategies play a key role in the prevention of cervical intraepithelial neoplasia (CIN), but evidence on the HPV type-specific prevalence in CIN is limited. This multicentric study estimates the prevalence of high-risk HPV types in CIN cases and the associations of HPV infection patterns with high-grade CIN in China in 2017-2018. Population-based prevention strategies should give preference to HPV-16 and 18, and strategies for non-16/18 high-risk HPV are essential for the elimination of cervical cancer.

Convalescent plasma for coronavirus disease 2019: A boon or bane

Coronavirus disease 2019 (COVID-19) pandemic emergence has re-evaluated the functionality of the notable convalescent plasma transfusion (CPT). It is a source of neutralising antibodies, which when transfused into severe acute respiratory syndrome coronavirus 2 infected patients are believed to employ an antiviral effect, suppressing the replication of virus before the patients regain their own effective humoral immune responses. The major accepted mode of action of the CPT therapy is viremia clearance, that happens mostly between 10 and 14 days after infection. Hence, CPT has been administered to the recipients typically after the emergence of early symptoms for anticipating maximize the efficacy of the therapy. CPT has been used in treating viral diseases including measles, mumps, poliomyelitis, and influenza in the pre-vaccine era. More recently, it has been used as a treatment approach for influenza, Ebola virus disease, and severe acute respiratory syndrome coronavirus epidemics, with varying success. The available evidence till date suggests that convalescent plasma which is collected from the COVID 19 survivors contains “receptor binding domain specific antibodies” possessing potent antiviral activity. Multicentred and well-designed clinical trial studies in establishing the efficacy of CPT among COVID-19 patients are being conducted globally. PubMed, EMBASE, and Medline databases were screened till November 01, 2020. This is an attempt to review studies of convalescent plasma on clinical outcomes in patients with COVID-19. From the outcomes of some of the completed studies, it is suggested that CPT therapy among COVID-19 patients seems to be safe and clinically efficacious to some extent.

Newly diagnosed Glioblastoma Multiforme (GBM) during COVID-19 pandemic: changes in therapeutic approach to minimize in-hospital SARS-COV-2 contagion in pre-vaccine era.

COVID-19 pandemic revolutionized how cancer patients are treated worldwide. Regarding neuro-oncological patients, usually considered frail and with lower life expectancy than other oncological patients, the international scientific community had to urgently reorganize the treatment approach to minimize the risk of in-hospital contagious. For GBM patients, adjuvant treatments have been evaluated with even much more attention to the expected efficacy. As a consequence, a hypofractionated radiotherapy regimen has been preferred to reduce the daily hospital accesses and, especially in pMGMT unmethylated patients, chemotherapy with Temozolomide was avoided. Here, we made a comprehensive evaluation of the neurooncological community suggestions regarding GBM treatment in the pre-vaccine era of the COVID-19 pandemic. (www.actabiomedica.it)

Haemophilus Influenzae Type B-Diseases

Haemophilus influenzae is a small Gram negative coccobacillus colonizing the respiratory tract of humans. The bacterium may cause direct local infections like otitis media, as well as severe invasive diseases like meningitis. In the prevaccine era, of the 6 capsular serotypes (a–f), type b caused the majority of invasive disease cases, whereas “nontypeable H. influenzae” (NTHi) and other capsular types predominate today. H. influenzae infections affect mainly children <5 years as well as persons >60 years with underlying diseases like COPD. Diagnosis of Hib disease is performed by classical microbiological culture techniques, antigen detection tests and polymerase chain reaction from blood samples, CSF or puncture samples. If untreated or if treatment is delayed, invasive Hib diseases may result in severe consequences such as hearing loss, chronic seizures, learning disabilities, and even death. Safe and effective polysaccharide-conjugate vaccines have been available for children for almost 30 years, reducing invasive Hib-incidences from about 60 to <1 / 105. Today, largely DTP-based Hib-combinations are used. After the primary series with 2 or 3 doses depending on the product and local recommendations, a booster dose in the second year of life is needed to ensure long-term protection.

Modeling serological testing to inform relaxation of social distancing for COVID-19 control

Serological testing remains a passive component of the public health response to the COVID-19 pandemic. Using a transmission model, we examine how serological testing could have enabled seropositive individuals to increase their relative levels of social interaction while offsetting transmission risks. We simulate widespread serological testing in New York City, South Florida, and Washington Puget Sound and assume seropositive individuals partially restore their social contacts. Compared to no intervention, our model suggests that widespread serological testing starting in late 2020 would have averted approximately 3300 deaths in New York City, 1400 deaths in South Florida and 11,000 deaths in Washington State by June 2021. In all sites, serological testing blunted subsequent waves of transmission. Findings demonstrate the potential benefit of widespread serological testing, had it been implemented in the pre-vaccine era, and remain relevant now amid the potential for emergence of new variants.

Immature Platelets and Disease Severity in Patients Hospitalized with Acute COVID-19 Who Are Vaccinated Against COVID-19

Introduction: COVID-19 has killed more than four million people worldwide and resulted in strained health resources globally(Dong Lancet ID 2020). There is a critical need for prognostic biomarkers to predict severity and outcomes in COVID-19 patients to allow more efficient resource allocation. Studies using pre-vaccination hospitalized patient data have demonstrated that elevated initial and peak immature platelet fraction (IPF), as well as related platelet indices, were associated with progression to severe COVID-19 outcomes (Welder Br J Haem 2021). This suggests the potential role of immature platelets as a cost-effective biomarker. The underlying pathophysiology of immature platelets in COVID-19 is unclear but these results support the hypothesis of higher inflammatory response, leading to thrombopoiesis mediated by pro-inflammatory cytokines and platelet hyper-reactivity in this population (Manne Blood 2021). It is unclear if this holds true in patients vaccinated against COVID-19. This study aims to assess the relationship between immature platelets in patients vaccinated against COVID-19 and hospitalized with acute COVID-19.Methods: This study used a COVID-19 patient registry established by the University of Texas Southwestern that comprises patients between May 2020 to July 2021. The database was approved by the Institutional Review Board. The study included 22 fully vaccinated adult patients with the mRNA COVID-19 vaccines hospitalized with acute COVID-19 and had IPF measurements during the hospitalization as well as 519 non-intensive care unit (ICU) patients admitted with acute COVID-19 prior to availability of a COVID-19 vaccine (pre-vaccination era). The study conducted non-parametric tests to compare hospital outcomes and covariates of interest between vaccinated patients and pre-vaccination era non-ICU patients. Covariates included for analysis are age, gender, race, length of hospital stay (LOS), dexamethasone use, platelet count, immature platelet count (IPC), IPF, thrombotic events and mortality.Results: All patients vaccinated against COVID-19 were alive without thrombotic events at the time of analysis. One out of 22 vaccinated patients required ICU admission and use of a ventilator. IPF and platelet counts at admission were similar between vaccinated patients and non-ICU patients from pre-vaccine era while IPC was significantly lower in the vaccinated group (Table 1). The vaccinated patient requiring ICU admission and mechanical ventilation was a heavy tobacco user with chronic obstructive pulmonary disease (IPF 6.1%, IPC 4x10 9/L, platelet count 66x10 9/L). There was a disproportionate number of Hispanic patients in the vaccinated cohort (44%, P = 0.02). The LOS was significantly shorter in vaccinated patients compared to pre-vaccination era non-ICU patients by a day and a half (P = 0.047). The admission IPF and IPC were not correlated with increased LOS (IPF Spearman ρ = 0.23, P = 0.31; IPC ρ = -0.34, P = 0.13), while platelet count at admission negatively correlated with LOS (ρ = -0.41, P = 0.06).Discussion: IPF, IPC, and platelet count have previously been demonstrated to be a predictor of increased ICU and hospital LOS, ventilator duration, and in-hospital mortality. To our knowledge, this is the first study assessing the relationship between IPF and platelet indices in hospitalized patients vaccinated against COVID-19. Due to the lack of severe COVID-19 outcomes in these vaccinated patients, LOS was the only variable able to be analyzed and lower platelet count was found to be associated with increased LOS . These preliminary results demonstrated similar initial IPF and platelet counts but lower IPC in a small cohort of vaccinated COVID-19 patients compared with the pre-vaccination era patients with no severe outcomes. This suggests that the predictive value of these biomarkers may also apply to the vaccinated patient population. As IPC in this current study is derived from IPF and platelet counts, independent measure of IPC is needed to confirm this finding in a larger cohort. This study also potentially suggests the protective benefits of COVID-19 vaccines as reported in prior randomized trials (Polack NEJM 2020). Further research is needed to confirm these findings in a larger vaccinated cohort assessing severe outcomes, hospitalization, and death, especially with future infection waves with contagious COVID-19 variants rapidly emerging. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Factors associated with COVID-19 vaccination acceptance among industrial workers in the post-vaccination era: a large-scale cross-sectional survey in China

ABSTRACT Background COVID-19 pandemic continues to pose a huge threat to public health. Mass vaccination is needed to achieve herd immunity against SARS-CoV-2. Currently, several vaccines are being inoculated on a large-scale. The willingness of COVID-19 vaccination had been well investigated in the pre-vaccination era, but no reported data in the post-vaccination era yet. Methods We conducted a large-scale survey among industrial workers during the vaccination campaign in China. Chi-square test and rank sum test were used to identify differences for various intentions regarding COVID-19 vaccination. Univariate analysis and multivariate regression models were utilized to analyze the relationship among demographic factors, related influencing factors and acceptance of COVID-19 vaccination. Results A total of 23,940 industrial workers were included, 66.0% were willing to take COVID-19 vaccine, 16.6% were unwilling, and 17.4% were unsure. Participants were more likely to get vaccinated if they were male, aged 45–65, being good educated, married, or being recommended by doctors or nurses. Participants with strong risk perception of COVID-19 infection, strong confidence in COVID-19 vaccine, high attention to COVID-19 vaccine, good health status, bad health habit, and a history of vaccination within three months were also more likely to be vaccinated. Conclusions This study calls for more attention and health-related education among industrial workers to improve their acceptance of COVID-19 vaccination.

Prevalence of Asymptomatic SARS-CoV-2 Infection in the General Population of the Veneto Region: Results of a Screening Campaign with Third-Generation Rapid Antigen Tests in the Pre-Vaccine Era.

The aim of our study was to ascertain the prevalence of SARS-CoV-2 infection in the general population during a period of moderate risk, just before Italy started to implement its vaccination campaign. A third-generation antigenic nasal swab sample was collected by a healthcare provider, and all individuals testing positive subsequently had a nasopharyngeal swab for molecular testing; the result was used to calculate the positive predictive value. The population consisted of 4467 asymptomatic adults with a mean age of 46.8 ± 16.00 years. The 62.2% tested for the first time, while 37.8% had previously undergone a mean 2.2 tests for SARS-CoV-2. With 77 of our overall sample reporting they had previously tested positive for COVID-19 and 14 found positive on our screening test, the overall estimated prevalence of the infection was 0.31%. Nine of the 14 cases were confirmed on molecular testing with a PPV of 64.3%. The mean age of the individuals testing positive was 38.1 ± 17.4. Based on the timing of symptom onset, six of the above cases were classified as false negatives, and the adjusted estimated prevalence was 0.34%. Describing levels of infection in a general population seems to be very difficult to achieve, and the universal screening proved hugely expensive particularly in a low-prevalence situation. Anyway, it is only thanks to mass screening efforts that epidemiological data have been collected. This would support the idea that routine screening may have an impact on mitigating the spread of the virus in higher-risk environments, where people come into contact more frequently, as in the workplace.

Impact analysis of rotavirus vaccination in various geographic regions in Western Europe

BackgroundUniversal mass vaccination (UMV) against rotavirus has been implemented in many but not all European countries. This study investigated the impact of UMV on rotavirus incidence trends by comparing European countries with UMV: Belgium, England/Wales and Germany versus countries without UMV: Denmark and the Netherlands. MethodsFor this observational retrospective cohort study, time series data (2001–2016) on rotavirus detections, meteorological factors and population demographics were collected. For each country, several meteorological and population factors were investigated as possible predictors of rotavirus incidence. The final set of predictors were incorporated in negative binomial models accounting for seasonality and serial autocorrelation, and time-varying incidence rate ratios (IRR) were calculated for each age group and country separately. The overall vaccination impact two years after vaccine implementation was estimated by pooling the results using a random effects meta-analyses. Independent t-tests were used to compare annual epidemics in the pre-vaccination and post-vaccination era to explore any changes in the timing of rotavirus epidemics. ResultsThe population size and several meteorological factors were predictors for the rotavirus epidemiology. Overall, we estimated a 42% (95%-CI 23;56%) reduction in rotavirus incidence attributable to UMV. Strongest reductions were observed for age-groups 0-, 1- and 2-years (IRR 0.47, 0.48 and 0.63, respectively). No herd effect induced by UMV in neighbouring countries was observed. In all UMV countries, the start and/or stop and corresponding peak of the rotavirus season was delayed by 4–7 weeks. ConclusionsThe introduction of rotavirus UMV resulted in an overall reduction of 42% in rotavirus incidence in Western European countries two years after vaccine introduction and caused a change in seasonal pattern. No herd effect induced by UMV neighbouring countries was observed for Denmark and the Netherlands.

Pertussis (Whooping Cough)

Pertussis (whooping cough) is a respiratory infection caused by Bordetella pertussis. All ages are susceptible. In the prevaccine era, almost all children became infected. Pertussis is particularly dangerous in young infants, who account for practically all hospitalizations and deaths, but clinical disease is burdensome at any age. Widespread use of pertussis vaccines dramatically reduced cases, but concern over adverse reactions led to the replacement of standard whole-cell by acellular pertussis vaccines that contain only a few selected pertussis antigens and are far less reactogenic. Routine administration of acellular pertussis vaccines combined with diphtheria and tetanus toxoids is recommended in infancy with toddler and preschool boosters, at age 11, and during pregnancy. Boosting in the second half of every pregancy is critical to protection of the newborn. Waning of vaccine immunity over time has become an increasing concern, and several new pertussis vaccines are being evaluated to address this problem.

The Impact of COVID-19 on Kidney Transplant Recipients in Pre-Vaccination and Delta Strain Era: A Systematic Review and Meta-Analysis.

Herein, we performed a meta-analysis of published clinical outcomes of corona virus disease 2019 (COVID-19) in hospitalized kidney transplant recipients. A systematic database search was conducted between December 1, 2019 and April 20, 2020. We analyzed 48 studies comprising 3137 kidney transplant recipients with COVID-19. Fever (77%), cough (65%), dyspnea (48%), and gastrointestinal symptoms (28%) were predominant on hospital admission. The most common comorbidities were hypertension (83%), diabetes mellitus (34%), and cardiac disease (23%). The pooled prevalence of acute respiratory distress syndrome and acute kidney injury were 58% and 48%, respectively. Invasive ventilation and dialysis were required in 24% and 22% patients, respectively. In-hospital mortality rate was as high as 21%, and increased to over 50% for patients in intensive care unit (ICU) or requiring invasive ventilation. Risk of mortality in patients with acute respiratory distress syndrome (ARDS), on mechanical ventilation, and ICU admission was increased: OR = 19.59, OR = 3.80, and OR = 13.39, respectively. Mortality risk in the elderly was OR = 3.90; however, no such association was observed in terms of time since transplantation and gender. Fever, cough, dyspnea, and gastrointestinal symptoms were common on admission for COVID-19 in kidney transplant patients. Mortality was as high as 20% and increased to over 50% in patients in ICU and required invasive ventilation.

Prevalence, Pattern and Genetic Diversity of Rotaviruses among Children under 5 Years of Age with Acute Gastroenteritis in South Africa: A Systematic Review and Meta-Analysis.

Rotavirus is the most significant cause of severe acute gastroenteritis among children under 5 years of age, worldwide. Sub-Saharan Africa particularly bears the brunt of the diarrheal deaths. A meta-analysis was conducted on 43 eligible studies published between 1982 and 2020 to estimate the pooled prevalence of rotavirus infection and changes in the main rotavirus strains circulating before and after vaccine introduction among under-five children in South Africa. The pooled national prevalence of rotavirus infection was estimated at 24% (95% CI: 21–27%) for the pre-vaccination period and decreased to 23% (95% CI: 21–25%) in the post-vaccination period. However, an increased number of cases was observed in the KwaZulu-Natal (21–28%) and Western Cape (18–24%) regions post-vaccination. The most dominant genotype combinations in the pre-vaccine era was G1P[8], followed by G2P[4], G3P[8], and G1P[6]. After vaccine introduction, a greater genotype diversity was observed, with G9P[8] emerging as the predominant genotype combination, followed by G2P[4], G12P[8], and G1P[8]. The introduction of the rotavirus vaccine was associated with a reduction in the burden of rotavirus-associated diarrhea in South Africa, although not without regional fluctuation. The observed changing patterns of genotype distribution highlights the need for ongoing surveillance to monitor the disease trend and to identify any potential effects associated with the dynamics of genotype changes on vaccine pressure/failure.

Genital warts trends in Australian and overseas-born people in Australia: A cross-sectional trend analysis to measure progress towards control and elimination.

Background: Substantial declines in genital warts have been observed in countries with quadrivalent/nonavalent human papillomavirus (q/n HPV) vaccination programmes, with Australia showing the most pronounced and long-term reductions. No study has assessed progress towards elimination of genital warts in a nation-wide sample of patients, and migrants’ contribution to population-level control of genital warts. We assessed Australia's progress towards genital warts elimination by examining trends in diagnoses in Australian- and overseas-born patients of sexual health clinics (SHCs) across Australia.Methods: A cross-sectional trend analysis of new genital warts diagnoses among first-time patients of 34 SHCs, between 2004 and 2018, was performed. Rate ratios (RR) were calculated using Poisson regression models, for comparing trends in proportions of new genital warts diagnoses in Australian- and overseas-born patients during the pre-vaccination era (2004-2007) and the vaccination era (2008-2018), and by 2018 relative to 2004-2007.Findings: A total of 439,957 new patients (Australian-born: 230,230; overseas-born: 209,727) were seen at SHCs, 6•4% were diagnosed with genital warts (Australian-born: 7•1%; overseas-born: 5•6%). By 2018, there had been a 64% reduction in the proportion of all SHC patients with a genital warts diagnosis relative to 2004-2007 (RR: 0•36, 95% CI: 0•35-0•38). The decline was more pronounced at 72% (RR: 0•28, 95% CI: 0 •27-0•30) among Australian-born patients, with the greatest reduction in women and men aged <21 years, at 98% (RR: 0•02, 95% CI: 0•01-0•03) and 92% (RR: 0•08, 95% CI: 0•06-0•11), respectively. By 2018, there was a 49% reduction in the proportion of overseas-born patients diagnosed with genital warts (RR: 0•51, 95% CI:0•48-0•54), and a 21% reduction in overseas-born patients from countries with no or bivalent HPV (bHPV) vaccination programme (RR: 0•79, 95% CI: 0•71-0•90).Interpretation: The substantial reductions in Australian-born people is a testament to the efficacy of quadrivalent (qHPV) and nonavalent (nHPV) vaccines and the high and wide-spread vaccination coverage in Australia. However, population-wide elimination of genital warts in Australia is dependent on other countries initiating or expanding their own HPV vaccination programmes.Funding: The Australian Government Department of Health and Seqirus Australia.

COVID-19 in children and young adults with moderate/severe inborn errors of immunity in a high burden area in pre-vaccine era

BackgroundInformation regarding inborn error of immunity (IEI) as a risk factor for severe COVID-19 is scarce. We aimed to determine if paediatric patients with moderate/severe IEI got COVID-19 at the same level as the general population, and to describe COVID-19 expression. Material and methodsWe included patients with moderate/severe IEI aged 0–21 years old: cross-sectional study (June2020) to determine the prevalence of COVID-19; prospective study (January2020-January2021) including IEI patients with COVID-19. Assays used: nasopharyngeal swab SARS-CoV-2 PCR and SARS-CoV-2-specific immunoglobulins. ResultsSeven from sixty-five patients tested positive (prevalence: 10.7% (7%–13%)) after the first SARS-COV-2 wave and 13/15 patients diagnosed with COVID-19 had an asymptomatic/mild course. ConclusionsIn our area, prevalence of COVID-19 in moderate/severe IEI paediatric patients after the first wave was slightly higher than in the general population. The majority of patients presented a benign course, suggesting a possible protective factor related with age despite IEI.

A Review on Rubella Vaccine: Iran (1975-2010).

The first Attenuated rubella vaccine was developed by Parkman and Meyer in 1966. Ten years later in the 1975s, the rubella vaccine was developed in Razi Vaccine and serum research institute) RVSRI). In 1977, the rubella TAKAHASHI vaccine successfully passed the clinical trial and was initially used voluntarily only in the private sector. Since 1987, the administration of rubella as MMR (Measles/AIK-C; Rubella/TAKAHASHI; Mumps/HOSHINO) strain vaccine has been included in the immunization program in Iran. This review article focused on the development and production of the rubella TAKAHASHI/HDC vaccine in RVSRI. The herd immunity and rubella cases were investigated in the pre- and post-vaccine era. The effectiveness and proper coverage of the rubella vaccine led to the elimination of rubella from Iran in 2019. The current study aimed to assess local rubella vaccine manufacturing and its consequences on rubella elimination from Iran, using various search engines. A complete search was carried out in medical databases, including PubMed, Scopus, Web of Science, Scientific Information Database, IranMedex, Magiran, and Google Scholar. Within 1972-1975, Rubella TAKAHASHI/HDC vaccine was developed by RVSRI and successfully passed clinical trial in 1977. Over the four last decades (1980-2020), more than 40 million infants, young, and adults were vaccinated by million doses of local Rubella, measles-rubella (MR) or measles-mumps-rubella (MMR) vaccine in Iran. In 1972, the pre-vaccine era, the overall sensitivity to rubella infection was 69% in one-year-old Iranian children and 23% in childbearing women. The use of a safe, inexpensive, and effective vaccine increased herd immunity to 95% (85%-99%) in our country. During the last two decades, we have witnessed a 91% decline in the confirmed rubella cases, from 1124 in 2000 to 33 cases in 2018. The current article presented the process of vaccine development, tracked it through more than four decades, and discussed disease status before and after the rubella vaccine era, as well as the history of its elimination from Iran. The effectiveness of the local Razi Rubella vaccine resulted in a significant increase in seroprevalence in Iran. Expanded vaccination against rubella, usually with measles, has led to the elimination of Rubella from Iran as confirmed by World Health Organization in 2019.

SARS-CoV-2 Infection in Health Workers: Analysis from Verona SIEROEPID Study during the Pre-Vaccination Era.

Background: To report the baseline phase of the SIEROEPID study on SARS-CoV-2 infection seroprevalence among health workers at the University Hospital of Verona, Italy, between spring and fall 2020; to compare performances of several laboratory tests for SARS-CoV-2 antibody detection. Methods: 5299 voluntary health workers were enrolled from 28 April 2020 to 28 July 2020 to assess immunological response to SARS-CoV-2 infection throughout IgM, IgG and IgA serum levels titration by four laboratory tests. Association of antibody titre with several demographic variables, swab tests and performance tests (sensitivity, specificity, and agreement) were statistically analyzed. Results: The overall seroprevalence was 6%, considering either IgG and IgM, and 4.8% considering IgG. Working in COVID-19 Units was not associated with a statistically significant increase in the number of infected workers. Cohen’s kappa of agreement between MaglumiTM and VivaDiagTM was quite good when considering IgG only (Cohen’s kappa = 78.1%, 95% CI 74.0–82.0%), but was lower considering IgM (Cohen’s kappa = 13.3%, 95% CI 7.8–18.7%). Conclusion: The large sample size with high participation (84.7%), the biobank and the longitudinal design were significant achievements, offering a baseline dataset as the benchmark for risk assessment, health surveillance and management of SARS-CoV-2 infection for the hospital workforce, especially considering the ongoing vaccination campaign. Study results support the national regulator guidelines on using swabs for SARS-CoV-2 screening with health workers and using the serological tests to contribute to the epidemiological assessment of the spread of the virus.

Streptococcus Pneumoniae-Associated Hemolytic Uremic Syndrome in the Era of Pneumococcal Vaccine

Streptococcus pneumoniae-associated hemolytic uremic syndrome (Sp-HUS) is a serious complication of invasive pneumococcal disease that is associated with increased mortality in the acute phase and morbidity in the long term. Recently, Sp-HUS definition has undergone revision and cases are categorized as definite, probable, and possible, based on less invasive serological investigations that evaluate Thomsen-Friedenreich crypt antigen (T-antigen) activation. In comparison to the pre-vaccine era, Sp-HUS incidence seems to be decreasing after the introduction of 7-serotype valence and 13-serotype valence pneumococcal vaccines in 2000 and 2010, respectively. However, Sp-HUS cases continue to occur secondary to vaccine failure and emergence of non-vaccine/replacement serotypes. No single hypothesis elucidates the molecular basis for Sp-HUS occurrence, although pneumococcal neuraminidase production and formation of T-antigen antibody complexes on susceptible endothelial and red blood cells continues to remain the most acceptable explanation. Management of Sp-HUS patients remains supportive in nature and better outcomes are being reported secondary to earlier recognition, better diagnostic tools and improved medical care. Recently, the addition of eculizumab therapy in the management of Sp-HUS for control of dysregulated complement activity has demonstrated good outcomes, although randomized clinical trials are awaited. A sustained pneumococcal vaccination program and vigilance for replacement serotypes will be the key for persistent reduction in Sp-HUS cases worldwide.

Human papillomavirus seroprevalence in pregnant women following gender-neutral and girls-only vaccination programs in Finland: A cross-sectional cohort analysis following a cluster randomized trial.

Cervical cancer elimination through human papillomavirus (HPV) vaccination programs requires the attainment of herd effect. Due to its uniquely high basic reproduction number, the vaccination coverage required to achieve herd effect against HPV type 16 exceeds what is attainable in most populations. We have compared how gender-neutral and girls-only vaccination strategies create herd effect against HPV16 under moderate vaccination coverage achieved in a population-based, community-randomized trial. In 2007-2010, the 1992-1995 birth cohorts of 33 Finnish communities were randomized to receive gender-neutral HPV vaccination (Arm A), girls-only HPV vaccination (Arm B), or no HPV vaccination (Arm C) (11 communities per trial arm). HPV16/18/31/33/35/45 seroprevalence differences between the pre-vaccination era (2005-2010) and post-vaccination era (2011-2016) were compared between all 8,022 unvaccinated women <23 years old and resident in the 33 communities during 2005-2016 (2,657, 2,691, and 2,674 in Arms A, B, and C, respectively). Post- versus pre-vaccination-era HPV seroprevalence ratios (PRs) were compared by arm. Possible outcome misclassification was quantified via probabilistic bias analysis. An HPV16 and HPV18 seroprevalence reduction was observed post-vaccination in the gender-neutral vaccination arm in the entire study population (PR16 = 0.64, 95% CI 0.10-0.85; PR18 = 0.72, 95% CI 0.22-0.96) and for HPV16 also in the herpes simplex virus type 2 seropositive core group (PR16 = 0.64, 95% CI 0.50-0.81). Observed reductions in HPV31/33/35/45 seroprevalence (PR31/33/35/45 = 0.88, 95% CI 0.81-0.97) were replicated in Arm C (PR31/33/35/45 = 0.79, 95% CI 0.69-0.90). In this study we only observed herd effect against HPV16/18 after gender-neutral vaccination with moderate vaccination coverage. With only moderate vaccination coverage, a gender-neutral vaccination strategy can facilitate the control of even HPV16. Our findings may have limited transportability to other vaccination coverage levels. ClinicalTrials.gov number NCT00534638, https://clinicaltrials.gov/ct2/show/NCT00534638.

Resurgence of Subacute Sclerosing Panencephalitis: Case Series and Global Epidemiological Trends

AbstractResurgence of subacute sclerosing panencephalitis (SSPE)—case series and global epidemiological trends. We noted a recent increase in cases of SSPE admitted in our institute, even though they had received measles vaccination. We did a detailed study of our cases and compared with global epidemiological trends of SSPE in preimmunization and era of developed immunity. Out of total 23 cases of SSPE, 12 presented in the year 2017 alone, reflecting a steep rise in incidence. Sixteen patients had received measles vaccine and never had prior measles infection. Mean age of onset was 8.2 years and average time of progression to advanced stage of disease was 65 days. Global data showed similar trends, that is, earlier age of onset with a faster rate of progression in the postvaccination era as compared with prevaccine era. Possible mechanisms to account for this trend include an early wild measles infection in the critical age of 6 to 9 months, before vaccination. There is a changing epidemiological trend of SSPE in terms of lower age of onset and faster rate of progression, also reflected in global data. There is a need for multicenter studies to verify the findings and explore possible measures like lowering the age of measles vaccination to halt this alarming trend.

Unexpected Role of Rotavirus G3P[8] Infection in Causing Severe Diarrhea in a Major Tertiary Referral Hospital in the Prevaccine Era

Background: Rotavirus A species is associated with severe gastroenteritis in children. Rotavirus G1P[8] was the most prevalent genotype found in Kuwait in a study conducted between 2005 and 2006. The RotaTeq vaccine was included in the Kuwait national immunization program at the end of 2017. Objectives: Since there is no available data on the rotavirus genotypes circulating before the introduction of the vaccine, we conducted a study to investigate the role of rotaviruses in causing severe diarrhea in children hospitalized in a major tertiary referral hospital in Kuwait during the year 2016. Methods: Viral RNA was isolated from the stool samples of 101 children under five years of age, hospitalized for acute gastroenteritis. Rotavirus VP4 and VP7 dsRNA were detected by RT-PCR, and their partial sequences were analyzed by phylogenic analysis. Results: Rotavirus dsRNA was detected in 24.7% of children with median age of 1 year. The genotype G3P[8] accounted for 47% of cases, followed by G1P[8] (26%), G9P[8] (10.5%), G4P[8] (10.5%), and G9P[4] (5%). Only VP7 nucleotide sequences of rotavirus G3 or G4 type clustered in the same lineage as RotaTeq vaccine, while most VP4 nucleotide sequences of rotavirus P[8] type clustered in a different lineage compared to Rotarix and RotaTeq vaccines. Conclusions: Our findings highlight the role of rotavirus G3P[8] in causing severe diarrhea and invites future investigations to know whether the recent introduction of RotaTeq vaccine in Kuwait selects certain genotypes and subgenomic lineages.