Partially Neutralizing Potency against Emerging Genotype I Virus among Children Received Formalin-Inactivated Japanese Encephalitis Virus Vaccine

Background

Genotype I (GI) Japanese encephalitis virus (JEV) that replaced GIII virus has become the dominant circulating virus in Asia. Currently, all registered live and inactivated JEV vaccines are derived from genotype III viruses. In Taiwan, the compulsory JEV vaccination policy recommends that children receives four doses of formalin-inactivated Nakayama (GIII) JEV vaccine.

Methodology/Principal Findings

To evaluate the influence of genotype replacement on the post-vaccination viral neutralizing ability by GIII and GI viruses, the small panel of vaccinated-children serum specimens was assembled, and the reciprocal 50% plaque-reduction neutralizing antibody titers (PRNT₅₀) were measured against Nakayama vaccine strain, CJN GIII human brain isolate and TC2009-1 GI mosquito isolate. The seropositivity rate (PRNT₅₀≥1∶10) and geometric mean titers (GMT) against the TC2009-1 virus were the lowest among the three viruses. The protective threshold against the CJN and TC2009-1 viruses could only be achieved when the GMT against Nakayama virus was ≥1∶20 or ≥1∶80, respectively. Using undiluted vaccinees'' sera, the enhancement of JEV infection in K562 cells was observed in some low or non-neutralizing serum specimens.

Conclusions/Significance

Our preliminary study has shown that neutralizing antibodies, elicited by the mouse brain-derived and formalin-inactivated JEV Nakayama vaccine among a limited number of vaccinees, have reduced neutralizing capacity against circulating GI virus, but more detailed studies are needed to address the potential impact on the future vaccine policy.     

Global burden of influenza-associated lower respiratory tract infections and hospitalizations among adults: A systematic review and meta-analysis

BackgroundInfluenza illness burden is substantial, particularly among young children, older adults, and those with underlying conditions. Initiatives are underway to develop better global estimates for influenza-associated hospitalizations and deaths. Knowledge gaps remain regarding the role of influenza viruses in severe respiratory disease and hospitalizations among adults, particularly in lower-income settings.Methods and findingsWe aggregated published data from a systematic review and unpublished data from surveillance platforms to generate global meta-analytic estimates for the proportion of acute respiratory hospitalizations associated with influenza viruses among adults. We searched 9 online databases (Medline, Embase, CINAHL, Cochrane Library, Scopus, Global Health, LILACS, WHOLIS, and CNKI; 1 January 1996–31 December 2016) to identify observational studies of influenza-associated hospitalizations in adults, and assessed eligible papers for bias using a simplified Newcastle–Ottawa scale for observational data. We applied meta-analytic proportions to global estimates of lower respiratory infections (LRIs) and hospitalizations from the Global Burden of Disease study in adults ≥20 years and by age groups (20–64 years and ≥65 years) to obtain the number of influenza-associated LRI episodes and hospitalizations for 2016. Data from 63 sources showed that influenza was associated with 14.1% (95% CI 12.1%–16.5%) of acute respiratory hospitalizations among all adults, with no significant differences by age group. The 63 data sources represent published observational studies (n = 28) and unpublished surveillance data (n = 35), from all World Health Organization regions (Africa, n = 8; Americas, n = 11; Eastern Mediterranean, n = 7; Europe, n = 8; Southeast Asia, n = 11; Western Pacific, n = 18). Data quality for published data sources was predominantly moderate or high (75%, n = 56/75). We estimate 32,126,000 (95% CI 20,484,000–46,129,000) influenza-associated LRI episodes and 5,678,000 (95% CI 3,205,000–9,432,000) LRI hospitalizations occur each year among adults. While adults <65 years contribute most influenza-associated LRI hospitalizations and episodes (3,464,000 [95% CI 1,885,000–5,978,000] LRI hospitalizations and 31,087,000 [95% CI 19,987,000–44,444,000] LRI episodes), hospitalization rates were highest in those ≥65 years (437/100,000 person-years [95% CI 265–612/100,000 person-years]). For this analysis, published articles were limited in their inclusion of stratified testing data by year and age group. Lack of information regarding influenza vaccination of the study population was also a limitation across both types of data sources.ConclusionsIn this meta-analysis, we estimated that influenza viruses are associated with over 5 million hospitalizations worldwide per year. Inclusion of both published and unpublished findings allowed for increased power to generate stratified estimates, and improved representation from lower-income countries. Together, the available data demonstrate the importance of influenza viruses as a cause of severe disease and hospitalizations in younger and older adults worldwide.

In this meta-analysis, Kathryn E. Lafond and colleagues estimate the global hospitalisation burden from influenza infections in adults.     

Seroprotective Antibodies to 2011 Variant Influenza A(H3N2v) and Seasonal Influenza A(H3N2) among Three Age Groups of US Department of Defense Service Members

Background

In 2011, a new variant of influenza A(H3N2) emerged that contained a recombination of genes from swine H3N2 viruses and the matrix (M) gene of influenza A(H1N1)pdm09 virus. New combinations and variants of pre-existing influenza viruses are worrisome if there is low or nonexistent immunity in a population, which increases chances for an outbreak or pandemic.

Methods

Sera collected in 2011 were obtained from US Department of Defense service members in three age groups: 19–21 years, 32–33 years, and 47–48 years. Pre- and post-vaccination samples were available for the youngest age group, and postvaccination samples for the two older groups. Specimens were tested using microneutralization assays for antibody titers against H3N2v (A/Indiana/10/2011) and seasonal H3N2 virus (A/Perth/16/2009).

Results

The youngest age group had significantly (p<0.05) higher geometric mean titers for H3N2v with 165 (95% confidence interval [CI]: 105–225) compared with the two older groups, aged 32–33 and 47–48 years, who had geometric mean titers of 68 (95% CI: 55–82) and 46 (95% CI: 24–65), respectively. Similarly, the youngest age group also had the highest geometric mean titers for seasonal H3N2. In the youngest age group, the proportion of patients who seroconverted after vaccination was 12% for H3N2v and 27% for seasonal H3N2.

Discussion

Our results were similar to previous studies that found highest seroprotection among young adults and decreasing titers among older adults. The proportion of 19- to 21-year-olds who seroconverted after seasonal vaccination was low and similar to previous findings. Improving our understanding of H3N2v immunity among different age groups in the United States can help inform vaccination plans if H3N2v becomes more transmissible in the future.     

Hypertension awareness,treatment, and control and their association with healthcare access in the middle-aged and older Indian population: A nationwide cohort study

BackgroundHypertension is the most important cardiovascular risk factor in India, and representative studies of middle-aged and older Indian adults have been lacking. Our objectives were to estimate the proportions of hypertensive adults who had been diagnosed, took antihypertensive medication, and achieved control in the middle-aged and older Indian population and to investigate the association between access to healthcare and hypertension management.Methods and findingsWe designed a nationally representative cohort study of the middle-aged and older Indian population, the Longitudinal Aging Study in India (LASI), and analyzed data from the 2017–2019 baseline wave (N = 72,262) and the 2010 pilot wave (N = 1,683). Hypertension was defined as self-reported physician diagnosis or elevated blood pressure (BP) on measurement, defined as systolic BP ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg. Among hypertensive individuals, awareness, treatment, and control were defined based on self-reports of having been diagnosed, taking antihypertensive medication, and not having elevated BP, respectively. The estimated prevalence of hypertension for the Indian population aged 45 years and older was 45.9% (95% CI 45.4%–46.5%). Among hypertensive individuals, 55.7% (95% CI 54.9%–56.5%) had been diagnosed, 38.9% (95% CI 38.1%–39.6%) took antihypertensive medication, and 31.7% (95% CI 31.0%–32.4%) achieved BP control. In multivariable logistic regression models, access to public healthcare was a key predictor of hypertension treatment (odds ratio [OR] = 1.35, 95% CI 1.14–1.60, p = 0.001), especially in the most economically disadvantaged group (OR of the interaction for middle economic status = 0.76, 95% CI 0.61–0.94, p = 0.013; OR of the interaction for high economic status = 0.84, 95% CI 0.68–1.05, p = 0.124). Having health insurance was not associated with improved hypertension awareness among those with low economic status (OR = 0.96, 95% CI 0.86–1.07, p = 0.437) and those with middle economic status (OR of the interaction = 1.15, 95% CI 1.00–1.33, p = 0.051), but it was among those with high economic status (OR of the interaction = 1.28, 95% CI 1.10–1.48, p = 0.001). Comparing hypertension awareness, treatment, and control rates in the 4 pilot states, we found statistically significant (p < 0.001) improvement in hypertension management from 2010 to 2017–2019. The limitations of this study include the pilot sample being relatively small and that it recruited from only 4 states.ConclusionsAlthough considerable variations in hypertension diagnosis, treatment, and control exist across different sociodemographic groups and geographic areas, reducing uncontrolled hypertension remains a public health priority in India. Access to healthcare is closely tied to both hypertension diagnosis and treatment.

Jinkook Lee and colleagues investigate hypertension management and its association with healthcare access in middle-aged and older adults in India.     

Comparative Evaluation of MRSA Nasal Colonization Epidemiology in the Urban and Rural Secondary School Community of Kurdistan,Iraq

BackgroundTo study the nasal carriage rate of Staphylococcus aureus (S. aureus) (including methicillin-resistant strains) in secondary school community of the urban and rural districts of the Kurdistan region of Iraq, a cross-sectional population based survey was carried out in the city Duhok and rural areas of Amedya, Akre and Zakho.MethodsNasal swabs were obtained from nostrils of 509 students aged 14-23 years. Resistance to methicillin was assessed by Kirby-Bauer disk diffusion and agar dilution assay. Vancomycin sensitivity was also tested on Muller-Hinton agar.ResultsIt was found that the frequency of overall S. aureus nasal carriage (SANC) was 17.75% (90/509, CI₉₅, 14.58–21.42%). In urban areas, the carriage rate was 20.59% (49/239, CI₉₅, 15.64–26.29%), whereas it was 15.24% (41/270, CI₉₅, 11.17–20.10%) in rural districts. The frequency of methicillin-resistant S. aureus (MRSA) among the isolated strains was found to be 2.04% (1/49) and 21.95% (9/41) in urban and rural areas respectively. It was found that in urban residents, the odd ratio (OR) of acquiring SANC was 1.44 (CI₉₅, 0.91-2.27%) and risk ratio (RR) was at least 1.35 (CI₉₅, 0.92-1.96%) while OR decreased to 0.12 (CI₉₅, 0.01-0.96%) for MRSA carriage. Hence, the S. aureus carriage rate was higher in urban districts compared to rural areas while more MRSA were found in rural areas compared to urban districts. All studied strains were sensitive to vancomycin.ConclusionThis study provided baseline information for S. aureus nasal colonization in the region. Also, it showed that living in rural areas increased the odds of MRSA colonization. More attention should be paid to control MRSA colonization in rural communities.     

Economic Evaluation of Immunisation Programme of 23-Valent Pneumococcal Polysaccharide Vaccine and the Inclusion of 13-Valent Pneumococcal Conjugate Vaccine in the List for Single-Dose Subsidy to the Elderly in Japan

BackgroundCurrently in Japan, both 23-valent pneumococcal polysaccharide vaccine (PPSV–23) and 13-valent pneumococcal conjugate vaccine (PCV–13) are available for the elderly for the prevention of S. pneumoniae-related diseases. PPSV–23 was approved in 1988, while the extended use of PCV–13 was approved for adults aged 65 and older in June 2014. Despite these two vaccines being available, the recently launched national immunisation programme for the elderly only subsidised PPSV–23. The framework of the current immunisation programme lasts for five years. The elderly population eligible for the subsidised PPSV–23 shot for the 1st year are those aged 65, 70, 75, 80, 85, 90, 95 and ≥100. While from the 2nd year to the 5th year, those who will age 65, 70, 75, 80, 85, 90, 95 and 100 will receive the same subsidised shot.MethodsWe performed economic evaluations to (1) evaluate the efficiency of alternative strategies of PPSV–23 single-dose immunisation programme, and (2) investigate the efficiency of PCV–13 inclusion in the list for single-dose pneumococcal vaccine immunisation programme. Three alternative strategies were created in this study, namely: (1) current PPSV–23 strategy, (2) 65 to 80 (as “65–80 PPSV–23 strategy”), and (3) 65 and older (as “≥65 PPSV–23 strategy”). We constructed a Markov model depicting the S. pneumoniae-related disease course pathways. The transition probabilities, utility weights to estimate quality adjusted life year (QALY) and disease treatment costs were either calculated or cited from literature. Cost of per shot of vaccine was ¥8,116 (US$74; US$1 = ¥110) for PPSV–23 and ¥10,776 (US$98) for PCV–13. The model runs for 15 years with one year cycle after immunisation. Discounting was at 3%.ResultsCompared to current PPSV–23 strategy, 65–80 PPSV–23 strategy cost less but gained less, while the incremental cost-effectiveness ratios (ICERs) of ≥65 PPSV–23 strategy was ¥5,025,000 (US$45,682) per QALY gained. PCV–13 inclusion into the list for single-dose subsidy has an ICER of ¥377,000 (US$3,427) per QALY gained regardless of the PCV–13 diffusion level. These ICERs were found to be cost-effective since they are lower than the suggested criterion by WHO of three times GDP (¥11,000,000 or US$113,636 per QALY gained), which is the benchmark used in judging the cost-effectiveness of an immunisation programmne.ConclusionsThe results suggest that switching current PPSV–23 strategy to ≥65 PPSV–23 strategy or including PCV–13 into the list for single-dose subsidy to the elderly in Japan has value for money.     

Diagnostic accuracy of antigen detection in urine and molecular assays testing in different clinical samples for the diagnosis of progressive disseminated histoplasmosis in patients living with HIV/AIDS: A prospective multicenter study in Mexico

BackgroundThe progressive disseminated histoplasmosis (PDH) has been associated with severe disease and high risk of death among people living with HIV (PLWHIV). Therefore, the purpose of this multicenter, prospective, double-blinded study done in ten Mexican hospitals was to determine the diagnostic accuracy of detecting Histoplasma capsulatum antigen in urine using the IMMY ALPHA Histoplasma EIA kit (IAHE), clarus Histoplasma GM Enzyme Immunoassay (cHGEI IMMY) and MiraVista Histoplasma Urine Antigen LFA (MVHUALFA); as well as the Hcp100 and 1281-1283₂₂₀SCAR nested PCRs in blood, bone-marrow, tissue biopsies and urine.Methodology/Principal findingsWe included 415 PLWHIV older than 18 years of age with suspicion of PDH. Using as diagnostic standard recovery of H. capsulatum in blood, bone marrow or tissue cultures, or histopathological exam compatible, detected 108 patients (26%, [95%CI, 21.78–30.22]) with proven-PDH. We analyzed 391 urine samples by the IAHE, cHGEI IMMY and MVHUALFA; the sensitivity/specificity values obtained were 67.3% (95% CI, 57.4–76.2) / 96.2% (95% CI, 93.2–98.0) for IAHE, 91.3% (95% CI, 84.2–96.0) / 90.9% (95% CI, 87.0–94.0) for cHGEI IMMY and 90.4% (95% CI, 83.0–95.3) / 92.3% (95% CI, 88.6–95.1) for MVHUALFA.The Hcp100 nested PCR was performed on 393, 343, 75 and 297, blood, bone marrow, tissue and urine samples respectively; the sensitivity/specificity values obtained were 62.9% (95%CI, 53.3–72.5)/ 89.5% (95%CI, 86.0–93.0), 65.9% (95%CI, 56.0–75.8)/ 89.0% (95%CI, 85.2–92.9), 62.1% (95%CI, 44.4–79.7)/ 82.6% (95%CI, 71.7–93.6) and 34.9% (95%CI, 24.8–46.2)/ 67.3% (95%CI, 60.6–73.5) respectively; and 1281-1283₂₂₀SCAR nested PCR was performed on 392, 344, 75 and 291, respectively; the sensitivity/specificity values obtained were 65.3% (95% CI, 55.9–74.7)/ 58.8% (95%CI, 53.2–64.5), 70.8% (95%CI, 61.3–80.2)/ 52.9% (95%CI, 46.8–59.1), 71.4% (95%CI, 54.7–88.2)/ 40.4% (95%CI, 26.4–54.5) and 18.1% (95%CI, 10.5–28.1)/ 90.4% (95%CI, 85.5–94.0), respectively.Conclusions/SignificanceThe cHGEI IMMY and MVHUALFA tests showed excellent performance for the diagnosis of PDH in PLWHIV. The integration of these tests in clinical laboratories will certainly impact on early diagnosis and treatment.     

Host Factors and Biomarkers Associated with Poor Outcomes in Adults with Invasive Pneumococcal Disease

BackgroundInvasive pneumococcal disease (IPD) causes considerable morbidity and mortality. We aimed to identify host factors and biomarkers associated with poor outcomes in adult patients with IPD in Japan, which has a rapidly-aging population.MethodsIn a large-scale surveillance study of 506 Japanese adults with IPD, we investigated the role of host factors, disease severity, biomarkers based on clinical laboratory data, treatment regimens, and bacterial factors on 28-day mortality.ResultsOverall mortality was 24.1%, and the mortality rate increased from 10.0% in patients aged ˂50 years to 33.1% in patients aged ≥80 years. Disease severity also increased 28-day mortality, from 12.5% among patients with bacteraemia without sepsis to 35.0% in patients with severe sepsis and 56.9% with septic shock. The death rate within 48 hours after admission was high at 54.9%. Risk factors for mortality identified by multivariate analysis were as follows: white blood cell (WBC) count <4000 cells/μL (odds ratio [OR], 6.9; 95% confidence interval [CI], 3.7–12.8, p < .001); age ≥80 years (OR, 6.5; 95% CI, 2.0–21.6, p = .002); serum creatinine ≥2.0 mg/dL (OR, 4.5; 95% CI, 2.5–8.1, p < .001); underlying liver disease (OR, 3.5; 95% CI, 1.6–7.8, p = .002); mechanical ventilation (OR, 3.0; 95% CI, 1.7–5.6, p < .001); and lactate dehydrogenase ≥300 IU/L (OR, 2.4; 95% CI, 1.4–4.0, p = .001). Pneumococcal serotype and drug resistance were not associated with poor outcomes.ConclusionsHost factors, disease severity, and biomarkers, especially WBC counts and serum creatinine, were more important determinants of mortality than bacterial factors.     

Seroprevalence of IgG antibodies against SARS-CoV-2 among the general population and healthcare workers in India,June–July 2021: A population-based cross-sectional study

BackgroundIndia began COVID-19 vaccination in January 2021, initially targeting healthcare and frontline workers. The vaccination strategy was expanded in a phased manner and currently covers all individuals aged 18 years and above. India experienced a severe second wave of COVID-19 during March–June 2021. We conducted a fourth nationwide serosurvey to estimate prevalence of SARS-CoV-2 antibodies in the general population aged ≥6 years and healthcare workers (HCWs).Methods and findingsWe did a cross-sectional study between 14 June and 6 July 2021 in the same 70 districts across 20 states and 1 union territory where 3 previous rounds of serosurveys were conducted. From each district, 10 clusters (villages in rural areas and wards in urban areas) were selected by the probability proportional to population size method. From each district, a minimum of 400 individuals aged ≥6 years from the general population (40 individuals from each cluster) and 100 HCWs from the district public health facilities were included. The serum samples were tested for the presence of IgG antibodies against S1-RBD and nucleocapsid protein of SARS-CoV-2 using chemiluminescence immunoassay. We estimated the weighted and test-adjusted seroprevalence of IgG antibodies against SARS-CoV-2, along with 95% CIs, based on the presence of antibodies to S1-RBD and/or nucleocapsid protein. Of the 28,975 individuals who participated in the survey, 2,892 (10%) were aged 6–9 years, 5,798 (20%) were aged 10–17 years, and 20,285 (70%) were aged ≥18 years; 15,160 (52.3%) participants were female, and 21,794 (75.2%) resided in rural areas. The weighted and test-adjusted prevalence of IgG antibodies against S1-RBD and/or nucleocapsid protein among the general population aged ≥6 years was 67.6% (95% CI 66.4% to 68.7%). Seroprevalence increased with age (p < 0.001) and was not different in rural and urban areas (p = 0.822). Compared to unvaccinated adults (62.3%, 95% CI 60.9% to 63.7%), seroprevalence was significantly higher among individuals who had received 1 vaccine dose (81.0%, 95% CI 79.6% to 82.3%, p < 0.001) and 2 vaccine doses (89.8%, 95% CI 88.4% to 91.1%, p < 0.001). The seroprevalence of IgG antibodies among 7,252 HCWs was 85.2% (95% CI 83.5% to 86.7%). Important limitations of the study include the survey design, which was aimed to estimate seroprevalence at the national level and not at a sub-national level, and the non-participation of 19% of eligible individuals in the survey.ConclusionsNearly two-thirds of individuals aged ≥6 years from the general population and 85% of HCWs had antibodies against SARS-CoV-2 by June–July 2021 in India. As one-third of the population is still seronegative, it is necessary to accelerate the coverage of COVID-19 vaccination among adults and continue adherence to non-pharmaceutical interventions.

Manoj Murhekar and co-workers report on the seroprevalence of anti-SARS-CoV-2 antibodies in India.     

Influence of Serotonin Transporter Gene Polymorphisms and Adverse Life Events on Depressive Symptoms in the Elderly: A Population-Based Study

BackgroundDepression is common in the elderly. The role of genetic and environmental factors in modulating depressive symptoms is not clear.MethodsWe evaluated the influence of serotonin transporter gene polymorphisms and recent adverse life events on depressive symptoms in an elderly Italian population. We used data from “InveCe.Ab”, a population-based study of 1321 subjects aged 70–74 years. We used the 15-item Geriatric Depression Scale (GDS) to assess depressive symptoms–a GDS score ≥5 points (GDS≥5) indicated the presence of clinically relevant symptoms–and performed 5-HTTLPR and rs25531 genotyping to obtain the triallelic polymorphism of the serotonin transporter. We used the Geriatric Adverse Life Events Scale to measure adverse life events, and logistic regression models to evaluate the role of genotype and recent adverse life events in depressive symptoms, controlling for potential confounders and independent predictors.ResultsTwo hundred subjects (15.76%) had a GDS≥5. The 5-HTTLPR triallelic polymorphism was significantly associated with GDS≥5. Only S′S′ carriers showed an increased risk of depressive symptoms (OR_adj = 1.81, p = .022); one extra adverse life event increased this risk by 14% (p = .061) independently of genotype. Other factors significantly related to GDS≥5 were: female gender (OR_adj = 2.49, p < .001), age (OR_adj = 1.19, p = .007), a history of depression (OR_adj = 4.73, p < .001), and comorbidity (OR_adj = 1.23, p = .001). One extra adverse life event increased the risk of depressive symptoms by 57% (p = .005) only in the L′L′ carriers, while antidepressant intake was directly related to GDS≥5 in the L′S′ carriers (OR_adj = 2.46, p = .036) and borderline significant in the S′S′ carriers (OR_adj = 2.41, p = .081).DiscussionThe S′S′ genotype and recent exposure to adverse life events were independently associated with depressive symptoms. The S′S′ genotype, compared with the environment, exerted a predominant effect on depressive symptoms, suggesting that it reduces the efficacy of antidepressant therapy. We conclude that genetics may be an important risk factor for depressive symptoms in late adulthood.     

Socioeconomic Status and Other Related Factors of Seasonal Influenza Vaccination in the South Korean Adult Population Based on a Nationwide Cross-Sectional Study

PurposeWe investigated the association between seasonal influenza vaccination in South Korea and socioeconomic status (SES) as well as other potential related factors.MethodsThe study was based on data obtained in the Korea National Health and Nutrition Examination Survey from 2010 to 2011. Education level and household income were used as indicators for SES. Univariate and multiple logistic regression analyses were used to evaluate SES and other demographic variables as related factors for influenza vaccination, the primary outcome.ResultsHigher household income was positively associated with higher vaccine uptake in the younger (19–49 years) group [adjusted odds ratio (aOR) 1.55, 95% confidence interval (CI) 1.08–2.23], whereas the low-income and low-education group had increased vaccination coverage than the middle-income and middle-education group in the older (≥ 50 years) group (aOR 1.36, 95% CI 1.09–1.69). Current smokers tend to be unvaccinated in all age groups. Among individuals aged ≥ 50, older age, mild to moderate alcohol consumption, regular exercise, and having co-morbidities were positively associated with vaccination, while those who self-reported their health status as good were less likely to be vaccinated.ConclusionsThe relationship between SES and seasonal influenza vaccination coverage differed between the age groups throughout the adult South Korean population. Public health policies need to address these inequalities.     

Prevalence of seroprotection against the pandemic (H1N1) virus after the 2009 pandemic

Background

Before pandemic (H1N1) 2009, less than 10% of serum samples collected from all age groups in the Lower Mainland of British Columbia, Canada, showed seroprotection against the pandemic (H1N1) 2009 virus, except those from very elderly people. We reassessed this profile of seroprotection by age in the same region six months after the fall 2009 pandemic and vaccination campaign.

Methods

We evaluated 100 anonymized serum samples per 10-year age group based on convenience sampling. We measured levels of antibody against the pandemic virus by hemagglutination inhibition and microneutralization assays. We assessed geometric mean titres and the proportion of people with seroprotective antibody levels (hemagglutination inhibition titre ≥ 40). We performed sensitivity analyses to evaluate titre thresholds of 80, 20 and 10.

Results

Serum samples from 1127 people aged 9 months to 101 years were obtained. The overall age-standardized proportion of people with seroprotective antibody levels was 46%. A U-shaped age distribution was identified regardless of assay or titre threshold applied. Among those less than 20 years old and those 80 years and older, the prevalence of seroprotection was comparably high at about 70%. Seroprotection was 44% among those aged 20–49 and 30% among those 50–79 years. It was lowest among people aged 70–79 years (21%) and highest among those 90 years and older (88%).

Interpretation

We measured much higher levels of seroprotection after the 2009 pandemic compared than before the pandemic, with a U-shaped age distribution now evident. These findings, particularly the low levels of seroprotection among people aged 50–79 years, should be confirmed in other settings and closer to the influenza season.In a previous age-based survey of about 1000 anonymized serum samples collected before substantial pandemic (H1N1) 2009 activity in the Lower Mainland of the province of British Columbia, Canada, we found that less than 10% of children and adults under 70 years of age had seroprotective levels of antibody against the pandemic (H1N1) virus.¹ This proportion was slightly higher among people aged 70–79 years (27%) and substantially higher among those above 80 years of age (77%).¹The 2009 influenza pandemic and the broad and effective vaccination campaign introduced major changes to this population’s immune status. The first wave in the province, in the spring and summer months, was of limited activity and was followed by a second, more substantial and widespread wave in the fall that peaked during the last week of October and resolved by the end of 2009.² Meanwhile, a highly immunogenic adjuvanted vaccine was provided free of charge through a universal vaccination campaign that targeted all Canadians.³ Supply was limited initially, requiring sequenced rollout of the vaccine, starting with children under five years of age, pregnant women, and people under 65 years who had comorbidities.⁴ The uptake of the vaccine of about 35%–45% in the province overall^4–6 and 44% in the Lower Mainland (Dr. Monika Naus, BC Centre for Disease Control, Vancouver, BC: personal communication, 2010) was estimated to be moderate compared with rates of uptake in other provinces.To assess seroprotective antibody levels after the 2009 pandemic, we repeated our age-based survey of antibody levels against the pandemic (H1N1) 2009 virus in a further 1000 serum samples collected from people in the Lower Mainland in May and June 2010, more than six months after the last peak of the epidemic.     

Understanding COVID-19 vaccine demand and hesitancy: A nationwide online survey in China

BackgroundThis study attempts to understand coronavirus disease 2019 (COVID-19) vaccine demand and hesitancy by assessing the public’s vaccination intention and willingness-to-pay (WTP). Confidence in COVID-19 vaccines produced in China and preference for domestically-made or foreign-made vaccines was also investigated.MethodsA nationwide cross-sectional, self-administered online survey was conducted on 1–19 May 2020. The health belief model (HBM) was used as a theoretical framework for understanding COVID-19 vaccination intent and WTP.ResultsA total of 3,541 complete responses were received. The majority reported a probably yes intent (54.6%), followed by a definite yes intent (28.7%). The perception that vaccination decreases the chances of getting COVID-19 under the perceived benefit construct (OR = 3.14, 95% CI 2.05–4.83) and not being concerned about the efficacy of new COVID-19 vaccines under the perceived barriers construct (OR = 1.65, 95% CI 1.31–2.09) were found to have the highest significant odds of a definite intention to take the COVID-19 vaccine. The median (interquartile range [IQR]) of WTP for COVID-19 vaccine was CNY¥200/US$28 (IQR CNY¥100–500/USD$14–72). The highest marginal WTP for the vaccine was influenced by socio-economic factors. The majority were confident (48.7%) and completely confident (46.1%) in domestically-made COVID-19 vaccine. 64.2% reported a preference for a domestically-made over foreign-made COVID-19 vaccine.ConclusionsThe findings demonstrate the utility of HBM constructs in understanding COVID-19 vaccination intent and WTP. It is important to improve health promotion and reduce the barriers to COVID-19 vaccination.     

Trends of Tuberculosis Case Notification and Treatment Outcomes in the Sidama Zone,Southern Ethiopia: Ten-Year Retrospective Trend Analysis in Urban-Rural Settings

BackgroundEthiopia is one of the high tuberculosis (TB) burden countries. An analysis of trends and differentials in case notifications and treatment outcomes of TB may help improve our understanding of the performance of TB control services.MethodsA retrospective trend analysis of TB cases was conducted in the Sidama Zone in southern Ethiopia. We registered all TB cases diagnosed and treated during 2003–2012 from all health facilities in the Sidama Zone, and analysed trends of TB case notification rates and treatment outcomes.ResultsThe smear positive (PTB+) case notification rate (CNR) increased from 55 (95% CI 52.5–58.4) to 111 (95% CI 107.4–114.4) per 10⁵ people. The CNRs of PTB+ in people older than 45 years increased by fourfold, while the mortality of cases during treatment declined from 11% to 3% for smear negative (PTB-) (X²_trend, P<0.001) and from 5% to 2% for PTB+ (X²_trend, P<0.001). The treatment success was higher in rural areas (AOR 1.11; CI 95%: 1.03–1.2), less for PTB- (AOR 0.86; CI 95%: 0.80–0.92) and higher for extra-pulmonary TB (AOR 1.10; CI 95%: 1.02–1.19) compared to PTB+. A higher lost-to-follow up was observed in men (AOR 1.15; CI 95%: 1.06–1.24) and among PTB- cases (AOR 1.14; CI 95%: 1.03–1.25). More deaths occurred in PTB-cases (AOR 1.65; 95% CI: 1.44–1.90) and among cases older than 65 years (AOR 3.86; CI 95%: 2.94–5.10). Lastly, retreatment cases had a higher mortality than new cases (6% vs 3%).ConclusionOver the past decade TB CNRs and treatment outcomes improved, whereas the disparities of disease burden by gender and place of residence reduced and mortality declined. Strategies should be devised to address higher risk groups for poor treatment outcomes.     

Rising Levels of HIV Infection in Older Adults in Eastern Zimbabwe

BackgroundWith the scale-up of antiretroviral treatment across Africa, many people are living longer with HIV. Understanding the ageing of the HIV cohort and sexual behaviour among older adults are important for appropriately responding to the changing demographics of people living with HIV.MethodsWe used data from a large population-based open cohort in eastern Zimbabwe to examine HIV prevalence trends and incidence among those aged 45 years and older. Five survey rounds have been completed between 1998 and 2011. Incidence was analysed using midpoint between last negative and first positive HIV test.ResultsAcross the survey rounds, 13,071 individuals were followed for 57,676 person years. While HIV prevalence among people aged 15–44 has fallen across the five rounds, HIV prevalence among those aged 45–54 has increased since the 2006–08 survey round. In the 2009–11 round, HIV prevalence among men aged 45–54 was 23.4% compared to 11.0% among those aged 15–44. HIV positive people aged 45–54 now represent more than 20% of all those living with HIV in Manicaland. Among those aged 45 years and older, there were 85 seroconversions in 11,999 person years for an HIV incidence of 0.708 per 100 person years. Analysis of cohort data and assessment of behavioural risk factors for HIV infection among older people shows significantly lower levels of condom use among older adults and a number of seroconversions past the age of 50.ConclusionsThe cohort of people living with HIV is ageing in Zimbabwe and the behaviour of older adults puts them at risk of HIV infection. Older adults must be included in both HIV prevention and treatment programs.     

Transmission and containment of the SARS-CoV-2 Delta variant of concern in Guangzhou,China: A population-based study

BackgroundThe first community transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant of concern (VOC) in Guangzhou, China occurred between May and June 2021. Herein, we describe the epidemiological characteristics of this outbreak and evaluate the implemented containment measures against this outbreak.Methodology/Principal findingsGuangzhou Center for Disease Control and Prevention provided the data on SARS-CoV-2 infections reported between 21 May and 24 June 2021. We estimated the incubation period distribution by fitting a gamma distribution to the data, while the serial interval distribution was estimated by fitting a normal distribution. The instantaneous effective reproductive number (R_t) was estimated to reflect the transmissibility of SARS-CoV-2. Clinical severity was compared for cases with different vaccination statuses using an ordinal regression model after controlling for age. Of the reported local cases, 7/153 (4.6%) were asymptomatic. The median incubation period was 6.02 (95% confidence interval [CI]: 5.42–6.71) days and the means of serial intervals decreased from 5.19 (95% CI: 4.29–6.11) to 3.78 (95% CI: 2.74–4.81) days. The incubation period increased with age (P<0.001). A hierarchical prevention and control strategy against COVID-19 was implemented in Guangzhou, with R_t decreasing from 6.83 (95% credible interval [CrI]: 3.98–10.44) for the 7-day time window ending on 27 May 2021 to below 1 for the time window ending on 8 June and thereafter. Individuals with partial or full vaccination schedules with BBIBP-CorV or CoronaVac accounted for 15.3% of the COVID-19 cases. Clinical symptoms were milder in partially or fully vaccinated cases than in unvaccinated cases (odds ratio [OR] = 0.26 [95% CI: 0.07–0.94]).Conclusions/SignificanceThe hierarchical prevention and control strategy against COVID-19 in Guangzhou was timely and effective. Authorised inactivated vaccines are likely to contribute to reducing the probability of developing severe disease. Our findings have important implications for the containment of COVID-19.     

MF59?-Adjuvanted H5N1 Vaccine Induces Immunologic Memory and Heterotypic Antibody Responses in Non-Elderly and Elderly Adults

Background

Pathogenic avian influenza virus (H5N1) has the potential to cause a major global pandemic in humans. Safe and effective vaccines that induce immunologic memory and broad heterotypic response are needed.

Methods and Findings

Healthy adults aged 18–60 and >60 years (n = 313 and n = 173, respectively) were randomized (1∶1) to receive two primary and one booster injection of 7.5 μg or 15 μg doses of a subunit MF59-adjuvanted H5N1 (A/Vietnam/1194/2004) (clade 1) vaccine. Safety was monitored until 6 months after booster. Immunogenicity was assessed by hemagglutination inhibition (HI), single radial hemolysis (SRH) and microneutralization assays (MN). Mild injection-site pain was the most common adverse reaction. No serious adverse events relating to the vaccine were reported. The humoral immune responses to 7.5 μg and 15 μg doses were comparable. The rates for seroprotection (HI>40; SRH>25mm²; MN ≥40) after the primary vaccination ranged 72–87%. Six months after primary vaccination with the 7.5 μg dose, 18% and 21% of non-elderly and elderly adults were seroprotected; rates increased to 90% and 84%, respectively, after the booster vaccination. In the 15 μg group, seroprotection rates among non-elderly and elderly adults increased from 25% and 62% after primary vaccination to 92% and 88% after booster vaccination, respectively. A heterologous immune response to the H5N1/turkey/Turkey/05 strain was elicited after second and booster vaccinations.

Conclusions

Both formulations of MF59-adjuvanted influenza H5N1 vaccine were well tolerated. The European Union requirement for licensure for pre-pandemic vaccines was met by the lower dose tested. The presence of cross-reactive antibodies to a clade 2 heterologous strain demonstrates that this vaccine may be appropriate for pre-pandemic programs.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00311480","term_id":"NCT00311480"}}NCT00311480     

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

BackgroundCervical 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.Methods and findingsIn 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 (PR_31/33/35/45 = 0.88, 95% CI 0.81–0.97) were replicated in Arm C (PR_31/33/35/45 = 0.79, 95% CI 0.69–0.90).ConclusionsIn 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.Trial registrationClinicalTrials.gov number {"type":"clinical-trial","attrs":{"text":"NCT00534638","term_id":"NCT00534638"}}NCT00534638, https://clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT00534638","term_id":"NCT00534638"}}NCT00534638.     

The Potential Use of Wolbachia-Based Mosquito Biocontrol Strategies for Japanese Encephalitis

Japanese encephalitis virus (JEV) is a zoonotic pathogen transmitted by the infectious bite of Culex mosquitoes. The virus causes the development of the disease Japanese encephalitis (JE) in a small proportion of those infected, predominantly affecting children in eastern and southern Asia. Annual JE incidence estimates range from 50,000–175,000, with 25%–30% of cases resulting in mortality. It is estimated that 3 billion people live in countries in which JEV is endemic. The virus exists in an enzootic transmission cycle, with mosquitoes transmitting JEV between birds as reservoir hosts and pigs as amplifying hosts. Zoonotic infection occurs as a result of spillover events from the main transmission cycle. The reservoir avian hosts include cattle egrets, pond herons, and other species of water birds belonging to the family Ardeidae. Irrigated rice fields provide an ideal breeding ground for mosquitoes and attract migratory birds, maintaining the transmission of JEV. Although multiple vaccines have been developed for JEV, they are expensive and require multiple doses to maintain efficacy and immunity. As humans are a “dead-end” host for the virus, vaccination of the human population is unlikely to result in eradication. Therefore, vector control of the principal mosquito vector, Culex tritaeniorhynchus, represents a more promising strategy for reducing transmission. Current vector control strategies include intermittent irrigation of rice fields and space spraying of insecticides during outbreaks. However, Cx. Tritaeniorhynchus is subject to heavy exposure to pesticides in rice fields, and as a result, insecticide resistance has developed. In recent years, significant advancements have been made in the potential use of the bacterial endosymbiont Wolbachia for mosquito biocontrol. The successful transinfection of Wolbachia strains from Drosophila flies to Aedes (Stegomyia) mosquitoes has resulted in the generation of “dengue-refractory” mosquito lines. The successful establishment of Wolbachia in wild Aedes aegypti populations has recently been demonstrated, and open releases in dengue-endemic countries are ongoing. This review outlines the current control methods for JEV in addition to highlighting the potential use of Wolbachia-based biocontrol strategies to impact transmission. JEV and dengue virus are both members of the Flavivirus genus, and the successful establishment of Drosophila Wolbachia strains in Cx. Tritaeniorhynchus, as the principal vector of JEV, is predicted to significantly impact JEV transmission.     

Cluster Survey Evaluation of a Measles Vaccination Campaign in Jharkhand,India, 2012

IntroductionIndia was the last country in the world to implement a two-dose strategy for measles-containing vaccine (MCV) in 2010. As part of measles second-dose introduction, phased measles vaccination campaigns were conducted during 2010–2013, targeting 131 million children 9 months to <10 years of age. We performed a post-campaign coverage survey to estimate measles vaccination coverage in Jharkhand state.MethodsA multi-stage cluster survey was conducted 2 months after the phase 2 measles campaign occurred in 19 of 24 districts of Jharkhand during November 2011–March 2012. Vaccination status of children 9 months to <10 years of age was documented based on vaccination card or mother’s recall. Coverage estimates and 95% confidence intervals (95% CI) for 1,018 children were calculated using survey methods.ResultsIn the Jharkhand phase 2 campaign, MCV coverage among children aged 9 months to <10 years was 61.0% (95% CI: 54.4–67.7%). Significant differences in coverage were observed between rural (65.0%; 95% CI: 56.8–73.2%) and urban areas (45.6%; 95% CI: 37.3–53.9%). Campaign awareness among mothers was low (51.5%), and the most commonly reported reason for non-vaccination was being unaware of the campaign (69.4%). At the end of the campaign, 53.7% (95% CI: 46.5–60.9%) of children 12 months to <10 years of age received ≥2 MCV doses, while a large proportion of children remained under-vaccinated (34.0%, 95% CI: 28.0–40.0%) or unvaccinated (12.3%, 95% CI: 9.3–16.2%).ConclusionsImplementation of the national measles campaign was a significant achievement towards measles elimination in India. In Jharkhand, campaign performance was below the target coverage of ≥90% set by the Government of India, and challenges in disseminating campaign messages were identified. Efforts towards increasing two-dose MCV coverage are needed to achieve the recently adopted measles elimination goal in India and the South-East Asia region.