Following the approval of Cervarix for the immunization of girls and women in China against high-risk human papillomavirus types 16 and 18, a non-interventional post-authorization safety study was performed. A multi-center prospective cohort study assessed safety following Cervarix vaccination of Chinese girls and women aged 9-45 years between 31 May 2018 and 3 December 2020. Adverse events following immunization (AEFIs), potential immune-mediated diseases (pIMDs), and pregnancy-related outcomes were collected up to 12 months from the third immunization or 24 months from the first immunization, whichever came first. Among 3,013 women who received 8,839 Cervarix doses, 167 (5.5%) reported >= 1 any AEFI, and 22 (0.7%) reported 40 serious AEFIs. During the 30 days after each dose, 147 women (4.9%) reported 211 medically attended AEFIs, including 3 serious AEFIs reported by 1 woman (0.03%). One woman reported a pIMD. Cervarix was inadvertently administered to 65 women (2.2%) within 60 days before conception or during pregnancy. Of these women, 34 (52.3%) gave birth to live infant(s) with no apparent congenital anomalies, and 1 (1.5%) woman gave birth to a live infant with a congenital anomaly. No serious AEFIs or pIMDs were considered to be related to the vaccination. In Chinese women aged 9-45 years, immunization with the Cervarix three-dose schedule was well tolerated. Overall, no safety concerns were identified, although rare adverse events may have been missed due to the study sample size.Clinical trial registration: NCT03438006. Infection with high-risk human papillomavirus is a prerequisite for cervical cancerCervarix is a human papillomavirus-16/18 AS04-adjuvanted vaccineMulti-centre prospective cohort study to monitor safety of Cervarix immunisationSafety was monitored in 3,013 girls/women aged 9-45 years in China (8,839 doses)Cervarix was well tolerated, and no safety concerns were identified

IntroductionHerpes zoster (HZ) chiefly affects older individuals and the immunocompromised and may lead to persistent pain, postherpetic neuralgia (PHN), and other complications.MethodsFrom 2012–2015, we conducted a prospective observational cohort study of adults ≥50 years with HZ presenting in primary care in Spain (NCT01521286). We estimated HZ incidence rates (IR) per 1,000 person-years (PY) over a 12-month period, and prospectively followed up a broader patient cohort; assessing pain severity using the ‘Zoster Brief Pain Inventory (ZBPI) and PHN development (defined as ZBPI ‘worst pain’ ≥3 at Day 90).ResultsHZ IR in adults ≥50 years was 4.88/1,000 PY (95% confidence interval [CI]: 4.44–5.35), similar for both genders. Incidence increased with age, from 2.54 (95% CI: 1.84–3.41) in 50–54-year-olds to 6.40/1,000 PY (95% CI: 4.86–8.28) in 75–79-year-olds. In 545 HZ patients followed prospectively, the proportion of HZ patients with PHN was 4.59% (95% CI: 2.99–6.70); and 11.79% (95% CI: 7.78–16.91) in those 212 patients with available ZBPI scores at Day 90. The proportion of patients developing PHN increased with increasing age. Mean ZBPI ‘worst pain’ scores in patients not developing PHN showed a marked decline between Day 0–30 (from 5.4 to 1.6) and none at Day 90; in patients with PHN this score remained high (>5.5) up to Day 150. Other complications were observed in 10.3% of patients.ConclusionsHZ presents a considerable burden in adults aged ≥50 years in Spain, with an IR of ~5/1,000 PY. HZ and PHN risk increased with age.

OBJECTIVE: To describe the clinical features of herpes zoster in adult patients treated at a large tertiary care hospital in Brazil over a 5-year period. METHODS: The medical records of suspected herpes zoster cases (based on ICD-10 codes) were identified for full review. Convenience sampling was used to select the medical records from a tertiary hospital in São Paulo. We collected data about co-existing medical conditions, medication use, herpes zoster-related clinical features and outcomes, and healthcare resource utilization. RESULTS: A total of 249 individuals whose first episode of herpes zoster occurred between 2010 and 2014 were included. The mean patient age was 55 years (range 18–96), and the majority were women (63.05%) and aged ≥ 50 years (63.86%). Medical comorbidities were reported in 92.77%, including diabetes (19.68%) and HIV infection (7.63%). Current/recent use of immunosuppressive agents was reported in 31.73%. A total of 65.86% of the patients were hospitalized: 102 patients (40.96%) were admitted for herpes zoster management, while 62 (24.90%) were already receiving inpatient care. The mean hospital length of stay was 16.60 days. One-third (34.14%) were managed as outpatients. Postherpetic neuralgia was reported as a complication in 18.07%. CONCLUSIONS: This retrospective descriptive study found a high frequency of herpes zoster episodes in older adults with comorbidities who sought medical care at a tertiary hospital. These results also underscore the importance of understanding the epidemiology of this disease and developing control strategies for these at-risk populations in Brazil.

[This corrects the article DOI: 10.1093/ofid/ofz486.].

Herpes zoster (HZ) mainly affects older adults and immunocompromised individuals and is usually characterized by a unilateral painful skin rash. Its most common complication, postherpetic neuralgia (PHN), may cause chronic debilitating pain lasting for months or years. This study (ClinicalTrials.gov Identifier: NCT01772160) aimed to estimate the HZ incidence and the proportion of HZ patients with PHN in the Italian population aged 50 years or older. From 2013 to 2016, HZ-patients were recruited when presenting with acute HZ at 75 reporting general practitioners in Italy, covering 43,875 persons aged >= 50 years. PHN was defined as 'worst pain' rated >= 3 on the Zoster Brief Pain Inventory persisting or appearing over 90 days after rash onset. The overall HZ incidence rate per 1000 person-years (PY) was estimated as 6.46 (95% confidence interval [CI]: 5.99-6.95), increasing with age to 9.12/1000 PY (95% CI: 7.50-10.99) in 75-79 year-olds. Among 391 HZ-patients who completed the study, the overall proportion with PHN was 10.23% (95% CI: 7.41-13.67) and the highest proportion was 15.56% (95% CI: 6.49-29.46) for the 75-79 year-olds. Among the 128 patients (32.7%) who reported at least one pre-existing medical condition, 35.9% reported diabetes mellitus and 32.0% reported emotional problems, stress or depression. The study confirms previous findings that HZ and PHN cause an important clinical burden in older Italian adults. It also confirmed the age-related increasing risk of HZ and PHN.

Objectives: Herpes zoster (HZ) mainly affects elderly people and immunocompromised individuals. HZ is usually characterized by a unilateral painful skin rash. Its most common complication, postherpetic neuralgia (PHN), may cause chronic debilitating pain. This study aimed to estimate the HZ incidence in individuals aged >= 50 years in Germany, the proportion of PHN and the economic burden. Methods: From 2010 to 2014, HZ patients were recruited when consulting physicians in physician networks covering about 157,000 persons aged >= 50 years. PHN was defined as "worst pain" rated >= 3 on the zoster brief pain inventory persisting or appearing over 90 days after rash onset. Costs were calculated based on medical resource utilization and lost working time. Results: HZ incidence was estimated as 6.7/1000 person-years, increasing with age to 9.4/1000 in >= 80 year-olds. Among 513 HZ patients enrolled, the proportion of PHN was 11.9%, rising with age to 14.3% in HZ patients >= 80 years. Estimated total cost per HZ patient was (sic) 156 from the healthcare system perspective and (sic) 311 from the societal perspective. Conclusions: The study confirmed previous findings that HZ causes a substantial clinical and economic burden in older German adults. It also confirmed the age-related increasing risk of HZ and PHN. (C) 2018 GlaxoSmithKline Biologicals SA. Published by Elsevier Ltd on behalf of The British Infection Association.

Background: Rotavirus (RV) is worldwide an important cause of acute gastroenteritis (AGE) in infants and young children. There is no specific treatment for AGE caused by RV (RVGE) but since 2006 two safe and effective vaccines have been available. RV vaccination was included in the national immunization program (NIP) of Latvia in 2015 with full reimbursement, and within the first year a coverage of 87% was achieved. This surveillance study was carried out to investigate the proportion of RVGE among AGE episodes in Latvia up to the inclusion of RV vaccination in the NIP to provide a basis for future assessments of the impact of RV vaccination. Methods: Prospective, one-year observational study of children younger than 5 years presenting with AGE in the primary care setting. At first primary care contact, a stool sample was collected and tested for RV using a rapid, visual immunochromatographic kit. The parents monitored their child’s symptoms over 2 weeks after the first contact and the investigator recorded these observations during a follow-up phone call. The proportion of RVGE among the AGE cases was estimated and the severity of each AGE case was assessed based on the recorded symptoms using the 20-point Vesikari scale. The seasonality of RVGE was also investigated. Results: Fifty-two primary care investigators collected data on 606 evaluable children with AGE. The proportion of RVGE was 38.1%. Severe AGE was experienced by 40.7% of the RV-positive and 19.5% of the RV-negative patients. The rate of hospitalization was 9.1% for the RV-positive and 4.8% for the RV-negative with no difference in the mean duration of hospital stays. AGE and RVGE both occurred all year round but with a clearly marked peak only for RVGE, from March to May. Conclusion: This study underlines that RV is an important cause of AGE in children under 5 years old in Latvia and that the burden of disease of RVGE in primary care was substantial before inclusion of RV vaccination in the NIP. Trial registration: NCT01733849

Background: In Nagoya city, Japan, rotavirus (RV) vaccination has been available since 2011 with estimated coverage reaching 92% by 2015 after the introduction of a public subsidy in 2012. This study assessed the impact of vaccination on the RV gastroenteritis (RVGE) burden in children aged <5 years old (y) by comparing RVGE hospitalizations and outpatient visits during pre-vaccination (2007-2011), transition (2011-2012) and subsidization (2012-2016) periods. Methods: All hospitalizations and outpatient visits in children aged <5 y from 2 administrative districts of Nagoya city were identified from the hospital-based electronic databases of 4 hospitals. RVGE cases were identified by diagnostic code and/or positive results of diagnostic kits. Results: Compared to the pre-vaccination period, there was a decrease in RVGE hospitalizations for children <5 y from 5.59 per 1000 person-year (kPY) to 3.65/kPY in the subsidization period (i.e. 34.69%). In children <1 y, the incidence of RVGE hospitalizations decreased continuously from 6.62/kPY in the pre vaccination period to 1.84/kPY in the subsidization period (i.e. 72.19%). The highest decrease was observed in the subsidization season i.e. when high coverage was reached: 69% and 75.57% in the 2013/2014 season for 2-3 y and 3-4 y, and 74.03% in the 2014/2015 season for 4-5 y, respectively. Proportion of RVGE outpatient visits decreased by 87.44% for children <1 y and 57.05% for <5 y from the pre-vaccination to the subsidization period. This decrease started the first year of subsidization for children <1 y, 1-2 y and 2-3 y (78.89%, 18.86% and 5.80%) and the second year (2013/2014 season) for children 3-4 y and 4-5 y (87.73% and 51.78%). Conclusions: Although yearly fluctuations have been observed, the introduction of vaccination significantly decreased pediatric RVGE hospitalizations and outpatient visits, especially in the age group eligible for vaccination. During the second and third year of subsidization, we observed a herd protection effect on other age groups <5 y who were not eligible for vaccination. (C) 2017 GlaxoSmithKline SA. Published by Elsevier Ltd.

To evaluate the safety of HPV‐16/18 AS04‐adjuvanted vaccine when administered as per the PI in Korea.

Epidemiological data on acute otitis media (AOM), an infectious disease frequently affecting children, are lacking in some countries. This study was undertaken to assess the incidence of AOM in children ≤5years in Saudi Arabia, Oman, Pakistan, and Turkey, as well as the economic burden from a parent/caregiver perspective. Medical records of 4043 children (Saudi Arabia=1023, Oman=998, Pakistan=1022, Turkey=1000) were retrospectively reviewed and the incidence of AOM episodes calculated from suspected and confirmed cases. Using a standardized Health Economics Questionnaire, parents recorded resource use and expenses incurred per AOM episode [in local currency and converted to US dollars (USD)]. The overall incidence of AOM episodes per 1000 person–years was: Saudi Arabia, 207 [95% confidence interval (CI): 178–238]; Oman, 105 (95% CI: 85–127); Pakistan, 138 (95% CI: 116–163); and Turkey, 99 (95% CI: 79–123). The mean total out-of-pocket healthcare expense incurred by parents/caregivers per episode was: Saudi Arabia USD67.1 [standard deviation (SD)=93.0], Oman USD16.1 (SD=16.4), Pakistan USD22.1 (SD=20.5), and Turkey USD33.6 (SD=44.9). The incidence of AOM episodes varied across all four countries, probably due to different diagnostic and management practices. Nevertheless, our results confirm that AOM causes a substantial burden to public health, reinforcing the need for cost-effective prevention strategies.

BACKGROUND:Rotavirus (RV) causes a high proportion of acute gastroenteritis (AGE) cases, especially among children under the age of five years old. This surveillance study was undertaken to study the incidence and severity of rotavirus gastroenteritis (RVGE) in primary care settings in Bulgaria over a one-year period.METHODS:In this prospective, observational study of AGE cases in children under five years of age presenting in the primary care setting over a one year period, stool samples were collected and tested for RV using a rapid visual immunochromatographic test kit. After the first visit, parents monitored their child for about two weeks and reported the symptoms experienced by the child during the follow-up period to the physician in a follow-up phone call. The percentage of RVGE cases among AGE was calculated and the severity of AGE (according to the 20-point Vesikari scale) was assessed by the physician based on the symptoms reported by the parents. The seasonality of RVGE was also studied.RESULTS:The proportion of RVGE among the 624 AGE cases examined was 25.5%. Severe AGE was experienced by 81.8% RV-positive and 54.6% RV-negative children (p-value <0.001) and a third of all severe AGE cases occurred in RV-positive patients. A multivariate logistic regression analysis of the determinants of hospitalization indicated that severity of disease and RV-positivity were the statistically significant variables explaining hospitalization of AGE cases; even controlling for severity, RV-positive patients were more often hospitalized than RV-negative ones. RVGE cases occurred throughout the year, with peaks during August and September.CONCLUSION:Our study emphasizes that RV is an important cause of AGE in children under five presenting in primary care settings in Bulgaria and a disproportionately high proportion of severe AGE cases may be attributed to RV infections.TRIAL REGISTRATION NUMBER:NCT01733849.

Approximately one in three persons will develop herpes zoster during their lifetime, and it can lead to serious complications such as postherpetic neuralgia. However, evidence on burden of herpes zoster and postherpetic neuralgia in Japan is limited. This prospective, observational, multicenter, physician practice‐based cohort study was conducted in Kushiro, Hokkaido, Japan (Clinicaltrials.gov identifier NCT01873365) to assess the incidence and hospitalization rates of herpes zoster, and the proportion, clinical burden and risk factors for postherpetic neuralgia in adults aged 60 years or more. Within the study area, 800 subjects developed herpes zoster and 412 were eligible for the study. Herpes zoster incidence was 10.2/1000 person‐years and higher among women and older subjects. Subjects with herpes zoster required on average 5.7 outpatient consultations. Herpes zoster‐associated hospitalization rate was 3.4% (27/800). The proportion of postherpetic neuralgia and other complications was 9.2% (38/412) and 26.5% (109/412), respectively. Statistically significant association with the development of postherpetic neuralgia was male sex (odds ratio [OR], 2.51; 95% confidence interval [CI], 1.17–5.38), age of 70–74 years (OR, 3.51; 95% CI, 1.09–11.3), immunosuppressive therapy (OR, 6.44; 95% CI, 1.26–32.9), severe herpes zoster pain at first consultation (OR, 3.08; 95% CI, 1.10–8.62) and rash on upper arms (vs no rash on upper arms; OR, 3.46; 95% CI, 1.10–10.9). Considerable herpes zoster and postherpetic neuralgia burden exists among elderly in Japan, and there may be predictive factors at the first visit which could be indicative of the risk of developing postherpetic neuralgia.

Background: Rotavirus (RV) vaccine, Rotarix, was introduced into the Brazil national immunization program in 2006. To estimate population-level vaccine effect, we conducted a time-trend analysis on all-cause gastroenteritis (GE)-related death certificate-reported deaths (DCRDs), hospital deaths (HDs) and hospitalizations trends in <5-year-olds before and after RV vaccine introduction.Methods: National level all-cause GE-related death certificate [Mortality Information System] and admission (Hospital Information System) data were aggregated and analyzed. Negative-binomial regression models (adjusting for age, year and region) compared DCRDs, HDs and hospitalization trends in <5-year-olds between baseline (2001-2005) and postvaccine introduction periods (Mortality Information System: 2007-2009 and Hospital Information System: 2007-2010). Negative-binomial regression models were fitted to data for each outcome before 2006, and the predicted annual frequencies of each outcome were plotted against corresponding observed annual frequencies.Results: During the postvaccine introduction period, there was an overall age-independent GE-related DCRDs reduction (20.9%, P = 0.04) observed in children < 5 years of age; a reduction was also seen in infants < 1 year of age (20.8%, P = 0.003). Age-independent GE-related HDs and hospitalizations reductions (57.1%, P < 0.0001 and 26.6%, P < 0.0001, respectively) were observed in < 5-year-olds; HDs reductions were also observed for each age group (< 1-year-olds: 55.0%, P < 0.0001 and 1- to < 5-year-olds: 59.5%, P < 0.0001). Observed annual frequencies of GE-related DCRDs, HDs and hospitalizations were lower than the predicted value in each age group in all years after 2006.Conclusions: GE-related DCRDs, HDs and hospitalizations were significantly reduced in < 1 and in 1- to <5-year-old Brazilian children after Rotarix introduction, which provides additional evidence of the direct and indirect population-level effect of RV vaccination on GE-related mortality and morbidity in children.

PURPOSE:Rotavirus (RV) is a leading cause of severe gastroenteritis (GE) in children across the world. As there is a lack of epidemiological data for RV gastroenteritis (RVGE) in Saudi Arabia, this hospital-based study was designed to estimate the disease burden of RVGE and assess the prevalent RV types in Saudi children younger than 5 years of age.PATIENTS AND METHODS:Children hospitalized for acute GE were enrolled at four pediatric referral hospitals in Saudi Arabia. The study was conducted from February 2007 to March 2008 and used the World Health Organization's generic protocol for RVGE surveillance. The Vesikari severity scale was used to assess the severity of RVGE. Stool samples were tested for RV using an enzyme-linked immunosorbent assay. Samples were further typed by reverse transcriptase-polymerase chain reaction and hybridization assay for determining the G and P types.RESULTS:A total of 1,007 children were enrolled; the final analysis included 970 children, of whom 395 were RV positive, 568 were RV negative, and seven had unknown RV status. The proportion of RVGE among GE hospitalizations was 40.7% (95% confidence interval: 37.6-43.9). The highest percentage of RVGE hospitalizations (83.1%) was seen in children younger than 2 years of age. The highest proportion of RV among GE hospitalizations was in June 2007 with 57.1%. The most common RV types detected were G1P[8] (49.3%), G1G9P[8] (13.2%), and G9P[8] (9.6%). Before hospitalization, severe GE episodes occurred in 88.1% RV-positive and 79.6% RV-negative children. Overall, 94% children had recovered by the time they were discharged. Two children (one RV positive and one RV negative) died due to GE complications.CONCLUSION:RVGE is responsible for a high proportion of hospitalizations in Saudi children younger than 5 years of age. Routine RV vaccination has therefore been introduced into the national immunization program and may help reduce the morbidity, mortality, and disease burden associated with RVGE in Saudi Arabia.

Human papillomavirus (HPV) is the necessary cause of cervical cancer. Published data on the epidemiology of HPV in women with invasive cervical cancer (ICC) in New Zealand (NZ) are limited. This cross-sectional study investigated the distribution of high-risk and low-risk HPV types in cervical specimens collected from women throughout NZ who had been diagnosed with ICC between 2004 and 2010.

Cervical cancer (CC) is caused by persistent infection with high-risk (HR) human papillomavirus (HPV) types. In Saudi Arabia which has a population of 6.5 million women over the age of 15 years, approximately 152 new cases of CC are diagnosed and 55 women die from the disease annually. Nevertheless current epidemiological data for HPV in this population are limited. This study evaluated the prevalence and type distribution of HPV and documented the awareness of HPV infection and health-related behavior among Saudi and non-Saudi women attending routine examination.

BACKGROUND:Cervical cancer ranks second among all cancers reported in Sri Lankan women. This study assessed the prevalence and type-distribution of human papillomavirus (HPV) among Sri Lankan women with invasive cervical cancer (ICC) and pre-cancerous lesions.METHODS:114 women aged 21 years and above, hospitalized in the National Cancer Institute, Sri Lanka with a diagnosis of ICC or cervical intraepithelial neoplasia (CIN) 2/3 were prospectively enrolled between October 2009 and September 2010 (110430/NCT01221987). The cervical biopsy or excision specimens collected during routine clinical procedures were subjected to histopathological review. DNA was extracted from samples with a confirmed histological diagnosis and was amplified using polymerase chain reaction and HPV DNA was detected using Enzyme Immuno Assay. HPV positive samples were typed using reverse hybridization Line Probe Assay.RESULTS:Of the cervical samples collected, 93.0% (106/114) had a histologically confirmed diagnosis of either ICC (98/106) or CIN 2/3 (8/106). Among all ICC cases, squamous cell carcinoma was diagnosed in the majority of women (81.6% [80/98]). HPV prevalence among ICC cases was 84.7% (83/98). The HPV types most commonly detected in ICC cases with single HPV infection (98.8% [82/83]) were HPV-16 (67.3%) and HPV-18 (9.2%). Infection with multiple HPV types was recorded in a single case (co-infection of HPV-16 and HPV-59).CONCLUSIONS:HPV was prevalent in most women with ICC in Sri Lanka; HPV-16 and HPV-18 were the predominantly detected HPV types. An effective prophylactic vaccine against the most prevalent HPV types may help to reduce the burden of ICC disease.

Persistent infection with high-risk (HR) human papillomavirus (HPV) causes cervical cancer, the fourth most frequent cancer in the Kingdom of Bahrain, with an annual incidence of four per 100,000 women. The aim of this study was to assess the prevalence and type distribution of HPV in Bahraini and non-Bahraini women attending routine screening. HPV prevalence was assessed by risk factors and age distribution. Health-related behaviors and HPV awareness were also studied.

Objectives: Persistent infection with high-risk (HR) human papillomavirus (HPV) is associated with premalignant lesions and cervical cancer, the third most common cancer amongst women globally and the second most frequent in Egypt. We studied the prevalence and type distribution of HPV and documented HPV infection awareness and health-related behaviours for HPV infection.Methods: This was a multicenter, hospital-based observational study of women >= 18 years of age who attended for a gynaecological examination during October 2010-August 2011. Cervical samples were tested using Linear Array HPV genotyping. Two questionnaires on awareness and health-related behaviour were completed.Results: Four hundred and forty-three women with a mean age of 39.3 +/- 14.0 years were included in the analysis. HPV DNA was detected in 10.4% of women; a single HPV-type infection was found in 6.5% and multiple infections in 3.8%. The most prevalent HR types among HPV-positive women were HPV-16 (19.6%) and HPV-31 and HPV-51 (15.2% each); low-risk types included HPV-62 (17.4%) and HPV-84 (10.9%). The prevalence of HPV-18 was low (6.5%). The prevalence of any HR HPV-type was highest in women aged 45-54 years (9.2%).Conclusions: The overall prevalence of HPV in Egypt was 10.4% and was highest (9.2%) amongst women aged 45-54 years. These data provide important reference information for public health authorities considering HPV prevention in Egypt. (C) 2014 Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.