Evaluation of Hepatitis A Vaccine in Post-Exposure Prophylaxis,The Netherlands, 2004-2012

Background

The secondary attack rate of hepatitis A virus (HAV) among contacts of cases is up to 50%. Historically, contacts were offered immunoglobulin (IG, a human derived blood product) as post-exposure prophylaxis (PEP). Amid safety concerns about IG, HAV vaccine is increasingly recommended instead. Public health authorities’ recommendations differ, particularly for healthy contacts ≥40 years old, where vaccine efficacy data is limited. We evaluated routine use of HAV vaccine as an alternative to immunoglobulin in PEP, in those considered at low risk of severe infection in the Netherlands.

Methods

Household contacts of acute HAV cases notified in Amsterdam (2004-2012) were invited ≤14 days post-exposure, for baseline anti-HAV testing and PEP according to national guidelines: immunoglobulin if at risk of severe infection, or hepatitis A vaccine if healthy and at low risk (aged <30, or, 30-50 years and vaccinated <8 days post-exposure). Incidence of laboratory confirmed secondary infection in susceptible contacts was assessed 4-8 weeks post-exposure. In a vaccinated subgroup, relative risk (RR) of secondary infection with estimated using Poisson regression.

Results

Of 547 contacts identified, 191 were susceptible to HAV. Per-protocol, 167 (87%) were vaccinated (mean:6.7 days post-exposure, standard deviation(sd)=3.3) and 24 (13%) were given immunoglobulin (mean:9.7 days post-exposure, sd=2.8). At follow-up testing, 8/112 (7%) had a laboratory confirmed infection of whom 7 were symptomatic. All secondary infections occurred in vaccinated contacts, and half were >40 years of age. In healthy contacts vaccinated per-protocol ≤8 days post-exposure, RR_{ref. ≤15 years} of secondary infection in those >40 years was 12.0 (95%CI:1.3-106.7).

Conclusions

Timely administration of HAV vaccine in PEP was feasible and the secondary attack rate was low in those <40 years. Internationally, upper age-limits for post-exposure vaccination vary. Pending larger studies, immunoglobulin should be considered PEP of choice in people >40 years of age and those vulnerable to severe disease.     

Sero-Molecular Epidemiology of Japanese Encephalitis in Zhejiang,an Eastern Province of China

BackgroundSporadic Japanese encephalitis (JE) cases still have been reported in Zhejiang Province in recent years, and concerns about vaccine cross-protection and population-level immunity have been raised off and on within the public health sphere. Genotype I (GI) has replaced GIII as the dominant genotype in Asian countries during the past few decades, which caused considerable concerns about the potential change of epidemiology characteristics and the vaccine effectiveness. The aim of this study was to investigate the prevalence of JE neutralizing antibody and its waning antibody trend after live attenuated JE vaccine immunization. Additionally, this study analyzed the molecular characteristics of the E gene of Zhejiang Japanese encephalitis virus (JEV) strains, and established genetic relationships with other JEV strains.Conclusion/SignificancesJE neutralizing antibody positive rates increase in age ≥10 years old population, likely reflecting natural infection or natural boosting of immunity through exposure to wild virus. JE seropositivity rates were quite low in <35 years old age groups in Zhejiang Province. Waning of neutralizing antibody after live attenuated vaccine immunization was observed, but the clinical significance should be further investigated. Both the peripheral antibody response and genetic characterization indicate that current live attenuated JE vaccine conferred equal neutralizing potency against GI or GIII of wild strains. GI has replaced GIII as the dominant genotype in Zhejiang in the past few decades. Although the chance of exposure to wild JE virus has reduced, the virus still circulates in nature; therefore, it is necessary to implement immunization program for children continually and to conduct surveillance activity periodically.     

国产甲型肝炎灭活疫苗用于儿童免疫效果研究

为了探讨国产甲型肝炎灭活疫苗在儿童中应用的免疫效果,选择2～15岁抗-HAV阴性健康易感儿童91名作为接种对象,采用0、6程序接种国产甲型肝炎灭活疫苗250U／剂,观察免疫后的局部反应和全身反应,并于全程免疫后一个月检测抗-HAV阳转率和抗体GMT。结果91例观察对象在初免和加强免疫后均未见即时副反应,只在8～72小时内出现轻微的一过性局部和全身反应。全程免疫后一个月抗-HAV阳转率为100％。抗体GMT为14 407mIU／ml。国产甲肝灭活疫苗在儿童中应用具有良好的安全性和免疫原性,采用0、6个月程序可获得高滴度抗体。     

Enhanced Mucosal Immune Responses Induced by a Combined Candidate Mucosal Vaccine Based on Hepatitis A Virus and Hepatitis E Virus Structural Proteins Linked to Tuftsin

Hepatitis A virus (HAV) and Hepatitis E virus (HEV) are the most common causes of infectious hepatitis. These viruses are spread largely by the fecal-oral route and lead to clinically important disease in developing countries. To evaluate the potential of targeting hepatitis A and E infection simultaneously, a combined mucosal candidate vaccine was developed with the partial open reading frame 2 (ORF2) sequence (aa 368–607) of HEV (HE-ORF2) and partial virus protein 1 (VP1) sequence (aa 1–198) of HAV (HA-VP1), which included the viral neutralization epitopes. Tuftsin is an immunostimulatory peptide which can enhance the immunogenicity of a protein by targeting it to macrophages and dendritic cells. Here, we developed a novel combined protein vaccine by conjugating tuftsin to HE-ORF2 and HA-VP1 and used synthetic CpG oligodeoxynucleotides (ODNs) as the adjuvant. Subsequent experiments in BALB/c mice demonstrated that tuftsin enhanced the serum-specific IgG and IgA antibodies against HEV and HAV at the intestinal, vaginal and pulmonary interface when delivered intranasally. Moreover, mice from the intranasally immunized tuftsin group (HE-ORF2-tuftsin + HA-VP1-tuftsin + CpG) showed higher levels of IFN-γ-secreting splenocytes (Th1 response) and ratio of CD4⁺/CD8⁺ T cells than those of the no-tuftsin group (HE-ORF2 + HA-VP1 + CpG). Thus, the tuftsin group generated stronger humoral and cellular immune responses compared with the no-tuftsin group. Moreover, enhanced responses to the combined protein vaccine were obtained by intranasal immunization compared with intramuscular injection. By integrating HE-ORF2, HA-VP1 and tuftsin in a vaccine, this study validated an important concept for further development of a combined mucosal vaccine against hepatitis A and E infection.     

Hepatitis a outbreak in a public school in Rio de Janeiro,Brazil

From June 1 to July 1 1999, an outbreak involving 25 cases of hepatitis A occurred in a public school in Rio de Janeiro, Brazil. Since these cases were notified to the State Health Department, the National Reference Center for Hepatitis Viruses (CNRHV) was required to investigate the extent of hepatitis A virus (HAV) dissemination. Blood samples from all students were tested for IgM and total anti-HAV antibodies using a commercial enzyme-linked immunoassay (ELISA). At the same time, a questionnaire was completed in order to identify possible risk factors for HAV infection. The environmental investigation showed that there was no fecal contamination of the water supply. The epidemiological investigation demonstrated that almost 50% of this population was susceptible to HAV infection and probably person-to-person transmission was the principal mode of virus dissemination. In this situation, a massive vaccination campaign could control the HAV infection.     

Effectiveness of HBV Vaccination in Infants and Prediction of HBV Prevalence Trend under New Vaccination Plan: Findings of a Large-Scale Investigation

Background

Hepatitis B virus (HBV) infection remains a severe public health problem. Investigating its prevalence and trends is essential to prevention.

Methods

To evaluate the effectiveness of HBV vaccination under the 1992 Intervention Program for infants and predicted HBV prevalence trends under the 2011 Program for all ages. We conducted a community-based investigation of 761,544 residents of 12 counties in Zhejiang Province selected according to their location, population density, and economic development. The HBV prevalence trends were predicted by a time-shifting approach. HBV surface antigen (HBsAg) and alanine amino transferase (ALT) were determined.

Results

Of the 761,544 persons screened for HBsAg, 54,132 were positive (adjusted carrier rate 6.13%); 9,455 had both elevated ALT and a positive HBsAg test (standardized rate 1.18%). The standardized HBsAg carrier rate for persons aged ≤20 years was 1.51%. Key factors influencing HBV infection were sex, age, family history, drinking, smoking, employment as a migrant worker, and occupation. With the vaccination program implemented in 2011, we predict that by 2020, the HBsAg carrier rate will be 5.27% and that for individuals aged ≤34 years will reach the 2% upper limit of low prevalence according to the WHO criteria, with a standardized rate of 1.86%.

Conclusions

The national HBV vaccination program for infants implemented in 1992 has greatly reduced the prevalence of HBV infection. The 2011 program is likely to reduce HBV infection in Zhejiang Province to a low moderate prevalence, and perinatal transmission is expected to be controlled by 2020.     

Routine Pediatric Enterovirus 71 Vaccination in China: a Cost-Effectiveness Analysis

BackgroundChina accounted for 87% (9.8 million/11.3 million) of all hand, foot, and mouth disease (HFMD) cases reported to WHO during 2010–2014. Enterovirus 71 (EV71) is responsible for most of the severe HFMD cases. Three EV71 vaccines recently demonstrated good efficacy in children aged 6–71 mo. Here we assessed the cost-effectiveness of routine pediatric EV71 vaccination in China.ConclusionsCompared to no vaccination, routine pediatric EV71 vaccination would be very cost-effective in China if the cost of immunization (including all logistical, procurement, and administration costs needed to confer 5 y of vaccine protection) is below US$12.0–US$18.3, depending on the choice of vaccine among the three candidates. Given that the annual number of births in China has been around 16 million in recent years, the annual costs for routine pediatric EV71 vaccination at this cost range should not exceed US$192–US$293 million. Our results can be used to determine the optimal vaccine when the prices of the three vaccines are known.     

Declining Trend of Hepatitis A Seroepidemiology in Association with Improved Public Health and Economic Status of Thailand

Hepatitis A virus (HAV) is transmitted via the fecal-oral route from contaminated food or water. As part of the most recent survey of viral hepatitis burden in Thailand, we analyzed the current seroprevalence of HAV in the country and compared with data dating back to 1971. From March to October, 2014, a total of 4,260 individuals between one month and 71 years of age from different geographical regions (North = 961; Central = 1,125; Northeast = 1,109; South = 1,065) were screened for anti-HAV IgG antibody using an automated chemiluminescent microparticle immunoassay. Overall, 34.53% (1,471/4,260) possessed anti-HAV IgG antibody, and the age-standardized seroprevalence was 48.6%. Seroprevalence rates were 27.3% (North), 30.8% (Central), 33.8% (Northeast) and 45.8% (South) and were markedly lower than in the past studies especially among younger age groups. The overall trend showed an increase in the age by which 50% of the population were anti-HAV IgG antibody: 4.48 years (1971–1972), 6 (1976), 12.49 (1990), 36.02 (2004) and 42.03 (2014).This suggests that Thailand is transitioning from low to very low HAV endemicity. Lower prevalence of HAV correlated with improved healthcare system as measured by decreased infant mortality rate and improved national economy based on increased GDP per capita. The aging HAV immuno-naïve population may be rendered susceptible to potential HAV outbreaks similar to those in industrialized countries and may benefit from targeted vaccination of high-risk groups.     

Relative transmissibility of shigellosis among different age groups: A modeling study in Hubei Province,China

Shigellosis is a heavy disease burden in China especially in children aged under 5 years. However, the age-related factors involved in transmission of shigellosis are unclear. An age-specific Susceptible–Exposed–Infectious/Asymptomatic–Recovered (SEIAR) model was applied to shigellosis surveillance data maintained by Hubei Province Centers for Disease Control and Prevention from 2005 to 2017. The individuals were divided into four age groups (≤ 5 years, 6–24 years, 25–59 years, and ≥ 60 years). The effective reproduction number (R_eff), including infectivity (R_I) and susceptibility (R_S) was calculated to assess the transmissibility of different age groups. From 2005 to 2017, 130,768 shigellosis cases were reported in Hubei Province. The SEIAR model fitted well with the reported data (P < 0.001). The highest transmissibility (R_eff) was from ≤ 5 years to the 25–59 years (mean: 0.76, 95% confidence interval [CI]: 0.34–1.17), followed by from the 6–24 years to the 25–59 years (mean: 0.69, 95% CI: 0.35–1.02), from the ≥ 60 years to the 25–59 years (mean: 0.58, 95% CI: 0.29–0.86), and from the 25–59 years to 25–59 years (mean: 0.50, 95% CI: 0.21–0.78). The highest infectivity was in ≤ 5 years (R_I = 1.71), and was most commonly transmitted to the 25–59 years (45.11%). The highest susceptibility was in the 25–59 years (R_S = 2.51), and their most common source was the ≤ 5 years (30.15%). Furthermore, “knock out” simulation predicted the greatest reduction in the number of cases occurred by when cutting off transmission routes among ≤ 5 years and from 25–59 years to ≤ 5 years. Transmission in ≤ 5 years occurred mainly within the group, but infections were most commonly introduced by individuals in the 25–59 years. Infectivity was highest in the ≤ 5 years and susceptibility was highest in the 25–59 years. Interventions to stop transmission should be directed at these age groups.     

Epidemiological Characteristics and Spatial-Temporal Clusters of Hand,Foot, and Mouth Disease in Zhejiang Province,China, 2008-2012

Hand, foot and mouth disease (HFMD) is one of the major public health concerns in China. Being the province with high incidence rates of HFMD, the epidemiological features and the spatial-temporal patterns of Zhejiang Province were still unknown. The objective of this study was to investigate the epidemiological characteristics and the high-incidence clusters, as well as explore some potential risk factors. The surveillance data of HFMD during 2008–2012 were collected from the communicable disease surveillance network system of Zhejiang Provincial Center for Disease Control and Prevention. The distributions of age, gender, occupation, season, region, pathogen’s serotype and disease severity were analyzed to describe the epidemiological features of HFMD in Zhejiang Province. Seroprevalence survey for human enterovirus 71 (EV71) in 549 healthy children of Zhejiang Province was also performed, as well as 27 seroprevalence publications between 1997 and 2015 were summarized. The spatial-temporal methods were performed to explore the clusters at county level. Furthermore, pathogens’ serotypes such as EV71 and coxsackievirus A16 (Cox A16) and meteorological factors were analyzed to explore the potential factors associated with the clusters. A total of 454,339 HFMD cases were reported in Zhejiang Province during 2008–2012, including 1688 (0.37%) severe cases. The annual average incidence rate was 172.98 per 100,000 (ranged from 72.61 to 270.04). The male-to-female ratio for mild cases was around 1.64:1, and up to 1.87:1 for severe cases. Of the total cases, children aged under three years old and under five years old accounted for almost 60% and 90%, respectively. Among all enteroviruses, the predominant serotype was EV71 (49.70%), followed by Cox A16 (26.05%) and other enteroviruses (24.24%) for mild cases. In severe cases, EV71 (82.85%) was the major causative agent. EV71 seroprevalence survey in healthy children confirmed that occult infection was common in children. Furthermore, literature summary for 26 seroprevalence studies during 1997–2015 confirmed that 0–5 years group showed lowest level of EV71 seroprevalence (29.1% on average) compared to the elder children (6–10 years group: 54.6%; 11–20 years group: 61.8%). Global positive spatial autocorrelation patterns (Moran’s Is>0.25, P<0.05) were discovered not only for mild cases but also for severe cases, and local positive spatial autocorrelation patterns were revealed for counties from the eastern coastal and southern regions. The retrospective space-time cluster analysis also confirmed these patterns. Risk factors analyses implied that more EV71 and less sunshine were associated with the clusters of HFMD in Zhejiang Province. Our study confirmed that Zhejiang Province was one of the highly epidemic provinces in China and that the epidemiological characteristics of HFMD were similar to other provinces. Occult infection in elder children and adults was one of the important reasons why most HFMD cases were children aged under-five. Combining the results of spatial autocorrelation analysis and the space-time cluster analysis, the major spatial-temporal clusters were from the eastern coastal and southern regions. The distribution of pathogens’ serotypes and the level of sunshine could be risk factors for, and serve as an early warning of, the outbreak of HFMD in Zhejiang Province.     

Immunogenicity,Impact on Carriage and Reactogenicity of 10-Valent Pneumococcal Non-Typeable Haemophilus influenzae Protein D Conjugate Vaccine in Kenyan Children Aged 1–4 Years: A Randomized Controlled Trial

Background

The impact on carriage and optimal schedule for primary vaccination of older children with 10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV) are unknown.

Methods

600 Kenyan children aged 12–59 months were vaccinated at days 0, 60 and 180 in a double-blind randomized controlled trial according to the following vaccine sequence: Group A: PHiD-CV, PHiD-CV, diphtheria/tetanus/acellular pertussis vaccine (DTaP); Group B: PHiD-CV, DTaP, PHiD-CV; Group C: hepatitis A vaccine (HAV), DTaP, HAV. Nasopharyngeal carriage of Streptococcus pneumoniae was measured at five timepoints. In 375 subjects, serotype-specific responses were measured by 22F-inhibition ELISA and opsonophagocytic killing assays (OPA) one month after vaccination.

Results

Following one dose of PHiD-CV, >90% of recipients developed IgG≥0.35 µg/mL to serotypes 1, 4, 5, 7F, 9V and 18C and OPA≥8 to serotypes 4, 7F, 9V, 18C, 23F. After a second dose >90% of recipients had IgG≥0.35 µg/mL to all vaccine serotypes and OPA≥8 to all vaccine serotypes except 1 and 6B. At day 180, carriage of vaccine-type pneumococci was 21% in recipients of two doses of PHiD-CV (Group A) compared to 31% in controls (p = 0.04). Fever after dose 1 was reported by 41% of PHiD-CV recipients compared to 26% of HAV recipients (p<0.001). Other local and systemic adverse experiences were similar between groups.

Conclusions

Vaccination of children aged 12–59 months with two doses of PHiD-CV two to six months apart was immunogenic, reduced vaccine-type pneumococcal carriage and was well-tolerated. Administration of PHiD-CV would be expected to provide effective protection against vaccine-type disease.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01028326","term_id":"NCT01028326"}}NCT01028326     

Disease Burden Due to Herpes Zoster among Population Aged ≥50 Years Old in China: A Community Based Retrospective Survey

ObjectiveTo understand the disease burden due to Herpes Zoster (HZ) among people aged ≥50 years old in China and provide baseline data for future similar studies, and provide evidence for development of herpes zoster vaccination strategy.MethodsRetrospective cohort study was conducted in 4 townships and one community. A questionnaire was used to collect information on incidence and cost of HZ among people aged ≥ 50 years old.ResultsThe cumulative incidence rate was 22.6/1,000 among people aged ≥ 50 years old. The average annual incidence rate of HZ was 3.43/1,000 among people aged ≥ 50 years old in 2010–2012. Cumulative incidence and average annual incidence rate increased with age: the cumulative incidence of HZ among people aged ≥ 80 years old was 3.34 times of that among 50- years old (52.3/1000vs15.7/1,000); average annual incidence rate rises from 2.66/1,000 among 50- years old to 8.55/1,000 among 80- year old. Cumulative incidence and average annual incidence rate for females were higher than that for males (cumulative incidence, 26.5/1000vs18.7/1,000; annual incidence rate, 3.95/1000vs2.89/1,000). Cumulative incidence and average annual incidence rate in urban were higher than in rural (cumulative incidence, 39.5/1000vs 17.2/1,000; annual incidence rate, 7.65/1000vs2.06/1,000). The hospitalization rate of HZ was 4.53%. And with the increase of age, the rate has an increasing trend. HZ costs 945,709.5 RMB in total, corresponding to 840.6 RMB per patient with a median cost of 385 RMB (interquartile range 171.7–795.6). Factors associated with cost included the first onset year, area, whether hospitalized and whether sequelae left.ConclusionIncidence rate, complications, hospitalization rate and average cost of HZ increase with age. We recommend that the HZ vaccinations should target people aged ≥50 years old if Zoster vaccine is licensed in China.     

Sporadic outbreaks of crimean-congo haemorrhagic fever in Uganda,July 2018-January 2019

IntroductionCrimean-Congo haemorrhagic fever (CCHF) is a tick-borne, zoonotic viral disease that causes haemorrhagic symptoms. Despite having eight confirmed outbreaks between 2013 and 2017, all within Uganda’s ‘cattle corridor’, no targeted tick control programs exist in Uganda to prevent disease. During a seven-month-period from July 2018-January 2019, the Ministry of Health confirmed multiple independent CCHF outbreaks. We investigated to identify risk factors and recommend interventions to prevent future outbreaks.MethodsWe defined a confirmed case as sudden onset of fever (≥37.5°C) with ≥4 of the following signs and symptoms: anorexia, vomiting, diarrhoea, headache, abdominal pain, joint pain, or sudden unexplained bleeding in a resident of the affected districts who tested positive for Crimean-Congo haemorrhagic fever virus (CCHFv) by RT-PCR from 1 July 2018–30 January 2019. We reviewed medical records and performed active case-finding. We conducted a case-control study and compared exposures of case-patients with age-, sex-, and sub-county-matched control-persons (1:4).ResultsWe identified 14 confirmed cases (64% males) with five deaths (case-fatality rate: 36%) from 11 districts in western and central region. Of these, eight (73%) case-patients resided in Uganda’s ‘cattle corridor’. One outbreak involved two case-patients and the remainder involved one. All case-patients had fever and 93% had unexplained bleeding. Case-patients were aged 6–36 years, with persons aged 20–44 years more affected (AR: 7.2/1,000,000) than persons ≤19 years (2.0/1,000,000), p = 0.015. Most (93%) case-patients had contact with livestock ≤2 weeks before symptom onset. Twelve (86%) lived <1 km from grazing fields compared with 27 (48%) controls (OR_M-H = 18, 95% CI = 3.2-∞) and 10 (71%) of 14 case-patients found ticks attached to their bodies ≤2 weeks before symptom onset, compared to 15 (27%) of 56 control-persons (OR_M-H = 9.3, 95%CI = 1.9–46).ConclusionsCCHF outbreaks occurred sporadically during 2018–2019, both within and outside ‘cattle corridor’ districts of Uganda. Most cases were associated with tick exposure. The Ministry of Health should partner with the Ministry of Agriculture, Animal Industry and Fisheries to develop joint nationwide tick control programs and strategies with shared responsibilities through a One Health approach.     

Ongoing Transmission of Hepatitis B Virus in Rural Parts of the Netherlands, 2009–2013

BackgroundReported acute hepatitis B incidence in the Netherlands reached its nadir in 2013. However, regional signals about increased number of hepatitis B cases raised the question how hepatitis B incidence was distributed over the country. In this study, regional differences in hepatitis B epidemiology were investigated using epidemiological and molecular data.MethodsAcute hepatitis B virus (HBV) infections, reported between 2009–2013, were included. If serum was available, a fragment of S and C gene of the HBV was amplified and sequenced. Regional differences in incidence were studied by geographical mapping of cases and cluster analysis. Regional differences in transmission were studied by constructing regional maximum parsimony trees based on the C gene to assess genetic clustering of cases.ResultsBetween 2009 and 2013, 881 cases were notified, of which respectively 431 and 400 cases had serum available for S and C gene sequencing. Geographical mapping of notified cases revealed that incidences in rural border areas of the Netherlands were highest. Cluster analysis identified two significant clusters (p<0.000) in the South-western and North-eastern regions. Genetic cluster analysis showed that rural border areas had relatively large clusters of cases with indistinguishable sequences, while other regions showed more single introductions.ConclusionThis study showed that regional differences in HBV epidemiology were present in the Netherlands. Rural border regions showed higher incidences and more ongoing transmission, mainly among MSM, than the more urban inland areas. Therefore, preventive measures should be enhanced in these regions.     

Seroepidemiology of hepatitis A virus infection in Japan: An area of very low endemicity

The incidence of hepatitis A virus (HAV) infection has declined significantly worldwide, including in Japan. A nationwide seroepidemiological study on hepatitis A in Japan has taken place almost every 10 years since 1973, and the last study was performed in 2003. In the present study, we describe the latest seroepidemiological pattern of hepatitis A in Japan using 7867 serum specimens obtained from healthy individuals collected between 2013 and 2017, approximately 10 years after the last study. Among them, 223 were anti-HAV positive. About 68% of individuals aged 60 years and older had anti-HAV antibodies, whereas only 1.1% of those aged below 60 years old had immunity; thus, almost all individuals younger than 60 years of age were HAV susceptible. In comparison with previous investigations, the susceptible population has increased and aged. According to data from the National Epidemiological Surveillance of Infectious Diseases (NESID) program, between 1989 and 2016, the proportion of patients with hepatitis A aged 60 years and older continuously increased with each year. The NESID data also suggested that recently, typical large foodborne outbreaks of hepatitis A have become rare, and cases tend to be reported among at-risk groups; overseas travelers contributed to 25% of hepatitis A cases, and in 2018, the first nationwide hepatitis A outbreak that affected mostly men who have sex with men was reported. The purpose of this study was to determine the current status of HAV infection in Japan, based on both seroepidemiology and the national surveillance data from the NESID.     

Factors associated with in-hospital mortality of adult tetanus patients–a multicenter study from Bangladesh

BackgroundTetanus, a vaccine-preventable disease, is still occurring in the elderly population of low- and middle-income countries with a high case-fatality rate. The objective of the study was to elucidate the factors associated with in-hospital mortality of tetanus in Bangladesh.MethodsThis prospective observational study, conducted in two specialized infectious disease hospitals, conveniently selected adult tetanus patients (≥18 years) for inclusion. Data were collected through a preformed structured questionnaire. Kaplan Meier survival analysis and univariate and multivariable Cox regression analysis were carried out to assess factors associated with in-hospital mortality among patients. All analysis was done using Stata (version 16) and SPSS (version 26).ResultsA total of 61 tetanus cases were included, and the overall in-hospital mortality rate was 34.4% (n = 21). Patients had an average age of 46.49 ±15.65 years (SD), and the majority were male (96.7%), farmers (57.4%), and came from rural areas (93.4%). Survival analysis revealed that the probability of death was significantly higher among patients having an age of ≥ 40 years, incubation time of ≤12 days, onset time of ≤ 4 days, and having complication(s). However, on multivariable Cox regression analysis, age (adjusted hazard ratio [aHR] 4.03, 95% Confidence Interval [CI] 1.07–15.17, p = 0.039) and onset time (≤4 days) (aHR 3.33; 95% CI 1.05–10.57, p = 0.041) came as significant predictors of in-hospital mortality after adjusting for incubation period and complications.ConclusionOlder age and short onset time are the two most important determinants of in-hospital mortality of tetanus patients. Hence, these patients require enhanced emphasis and care.     

2004—2013年深圳市乙型病毒性肝炎流行特征分析

目的了解深圳市乙型病毒性肝炎(乙肝)流行特征,为制定乙肝防控策略提供科学依据。方法用描述性流行病学方法对2004—2013年深圳市乙肝疫情资料进行分析。结果深圳市2004—2013年共报告乙肝病例90 292例,剔除慢性病例71 435例,年均报告发病率为19.72/10万,发病率最高年份2007年为33.29/10万,最低年份2013年为9.32/10万。发病年龄构成中,15岁占1.58%,15~44岁占89.91%,≥45岁占8.52%;以20~30岁为发病高峰期;男性多于女性,男女性别比为3.33∶1(14 503/4 354);工人发病数最多,占总病例数42.3%;市郊发病率高于市区。结论深圳市近6年乙肝发病率呈下降趋势;15岁儿童病例显著减少,表明乙肝疫苗接种成效显著。     

Effect of Pneumococcal Conjugate Vaccination in Uruguay,a Middle-Income Country

Background

In 2008, a 7-valent pneumococcal conjugate vaccine (PCV7) was introduced into the routine childhood immunization program in Uruguay, with a 2+1 schedule. In 2010, PCV13 replaced PCV7, and the same 2+1 schedule was used. The effect of these pneumococcal vaccines on the incidence of invasive pneumococcal infections (IPD) and on serotype distribution was analyzed retrospectively, based on passive national laboratory surveillance.

Methods

Data from 1,887 IPD isolates from 5 years before and 5 years after PCV7 introduction (7 before and 3 after PCV13 introduction) was examined to assess the incidence rate per 100,000 age-specific population of all IPD, PCV7-serotypes, and PCV13-serotypes associated IPD among children <2 years and 2 to 4 years old, and patients ≥5 years old. Trends of frequency for each serotype were also analyzed.

Results

Comparison of pre-vaccination (2003–2007) and post-vaccination (2008–2012) periods showed a significant decrease in IPD incidence among children <2 years old (IR 68.7 to IR 29.6, p<0.001) and children 2 to 4 years (p<0.04). IPD caused by serotypes in PCV7 was reduced by 95.6% and IPD caused by 6 serotypes added in PCV13 was reduced by 83.9% in children <5 years old. Indirect effects of both conjugate vaccines were observed among patients ≥5 years old one year after the introduction of each vaccine, in 2010 for PCV7 and in 2012 for PCV13. Nevertheless, for reasons that still need to be explained, perhaps due to ascertainment bias, total IPD in this group increased after 2007. In 2012, the relative frequency of vaccine serotypes among vaccinated and unvaccinated population declined, except for serotype 3. Non vaccine serotypes with increasing frequency were identified, in rank order: 12F, 8, 24F, 22F, 24A, 15C, 9N, 10A and 33.

Conclusion

Consecutive immunization with PCV7 and PCV13 has significantly reduced IPD in children <5 years of age in Uruguay.     

Twenty Years of Medically-Attended Pediatric Varicella and Herpes Zoster in Ontario,Canada: A Population-Based Study

ObjectiveTo determine if reductions in medically-attended pediatric varicella and herpes zoster occurred in Ontario, Canada, after publicly-funded varicella immunization was implemented in 2004.MethodsFor fiscal years (FY) 1992-2011, we examined data on varicella and herpes zoster physician office visits, emergency department (ED) visits, hospitalizations (including for varicella-associated skin and soft tissue infections [SSTI]), and intensive care unit (ICU) admissions, among those aged <18 years. The pre-vaccine, privately-available, and vaccine program eras were FY1992-1998, FY1999-2003, and FY2004-2011, respectively. We used Poisson regressionand Kruskal-Wallis tests (all at the p<0.05 level of significance), and compared rates using incidence rate ratios (IRRs) and 95% confidence intervals (CIs).ResultsIncidence of varicella office visits declined over the study period from a high of 25.1/1,000 in FY1994 to a low of 3.2/1,000 in FY2011. ED visits and hospitalizations followed similar patterns of decreasing rates later in the study period. IRRs comparing the vaccine program versus pre-vaccine eras were 0.29 (95%CI: 0.26-0.32) for office visits, 0.29 (95%CI: 0.21-0.40) for ED visits, and 0.41 (95%CI: 0.10-1.69) for hospitalizations. Annual declines in varicella office visits were 7.7%, 9.1%, 8.4%, and 8.4% per year among children aged <1 year, 1-4 years, 5-11 years, and ≥12 years, respectively (all p<0.001). Age-specific rates of varicella-associated SSTI declined significantly among children <12 years (p<0.001) and rates of ICU admissions decreased significantly for children <1 year (p = 0.02). (p<0.001) over the study period. For children aged 5-17 years, herpes zoster office visits decreased whereas ED visits increased (both p<0.001) and there was a small, non-significant (p = 0.07), decrease in hospitalizations.ConclusionMedically-attended varicella decreased during the study period, particularly since varicella vaccine was publicly-funded. Results suggest immunization program-related changes in varicella epidemiology, including herd effects, demonstrated by reductions in varicella in program-ineligible age groups. We did not observe a consistent impact on herpes zoster.     

Temporal-spatial distribution characteristics of leprosy: A new challenge for leprosy prevention and control in Zhejiang,China

BackgroundAfter the elimination of leprosy in 1995, there were 10–30 newly detected leprosy cases every year in Zhejiang Province, and the epidemiological characteristics of the newly detected leprosy cases have changed. While most of the newly detected cases came from other provinces in China, not Zhejiang, it brought a new challenge for leprosy prevention and control in post- elimination era in Zhejiang, China. This study was aimed to understand the temporal-spatial distribution characteristics of newly detected leprosy cases, and provide the scientific rationales for the development of leprosy control strategy.MethodsData on the demographic of Zhejiang Province from 2011 to 2019 were obtained from the China Information System for Disease Control and Prevention, and the epidemiological data on leprosy cases newly detected in Zhejiang Province from 2011 to 2019 were obtained from the LEPROSY MANAGEMANT INFORMATION SYSTEM IN CHINA (LEPMIS), and temporal-spatial distributions were described. The geographic information system software—ArcGIS 10.4 was used to draw the statistical maps, and Geoda 1.14.0 was used for local spatial autocorrelation analysis (local Getis coefficient method). Ridley-Jopling classification was used to classify the clinical types into I, TT, BT, BB, BL or LL. Two-group classification system developed by the World Health Organization (WHO) was used and cases were classified into multibacillary (MB) type or paucibacillary (PB) type.ResultsA total of 167 leprosy cases were reported in Zhejiang Province during 2011–2019, including 107 cases in males and 60 in females. The mean age at diagnosis was 37.99±14.81 years, and 94.01% of the cases were detected through the examination at skin-clinics. The number of workers, MB cases, G2D cases were 81 (48.50%), 159 (94.01%), 24 (14.37%) respectively, and the rate of early detection increased from 45.16% in 2011 to 90.91% in 2019. Leprosy cases were reported in all the prefectures of Zhejiang except Zhoushan City. The cases in local population accounted for 23.35% (39 cases), and the cases in floating population (especially coming from high epidemic provinces in China) accounted for 76.65% (128 cases). The annual number of newly detected cases showed a decreasing trend, from 31 cases in 2011 to 11 in 2019. Time of the floating population living in Zhejiang Province ranged from several months to more than 10 years. The annual proportion of new cases with G2D declined from 22.58% in 2011 to 9.09% in 2019. The results of local indicators of autocorrelation (LISA) analysis showed that the high-high areas were mainly concentrated in the middle and northeast of Zhejiang Province, while the low-low areas were in the east and southwest.ConclusionA few scattered cases still can be seen in post-elimination era, and there was a spatial clustering of the newly detected leprosy cases in Zhejiang Province. Most of the cases in Zhejiang Province were from other high epidemic provinces in China, which brought a new challenge for leprosy control and prevention in post- elimination era in Zhejiang, and it is also necessary to strengthen the early detection and standard management of the leprosy cases in floating population in Zhejiang.