Pneumococcal vaccination and primary care presentations for acute respiratory tract infection and antibiotic prescribing in older adults.

BACKGROUND: While the 23-valent pneumococcal polysaccharide vaccine (PPV23) has demonstrated its role in preventing severe pneumococcal disease, its impact on more non-specific conditions like acute respiratory tract infection (ARI) and lower respiratory tract infections (LRTI) remains unclear. We aimed to investigate the role of PPV23 in prevention of presentations for ARI and LRTI and related antibiotic prescriptions among older adults in primary care. METHODS: Using a nationwide general practice dataset, we followed a cohort of regularly attending patients aged ≥65 years from 1 January 2014 until 31 December 2018 for presentations for ARI, LRTI, and related antibiotic prescriptions. Associations between PPV23 receipt and each outcome were assessed using a multiple failures survival model to estimate hazard ratios (HR) adjusted for age, sex, socioeconomic status, and various health measures. RESULTS: A cohort of 75,264 patients aged ≥65 years (mean 75.4, 56% female) in 2014 was followed. The incidence of presentations for ARI, ARI-related antibiotic prescription, LRTI, and LRTI-related antibiotic prescription was 157.6, 76.0, 49.6, and 24.3 per 1000 person-years, respectively. Recent PPV23 vaccine receipt was associated with a small reduction in ARI presentations (adjusted HR vaccinated vs. unvaccinated 0.96; 95%CI 0.94-0.98; p = 0.002); however, there was no reduction in ARI-related antibiotic prescription, LRTI presentation, nor LRTI-related antibiotic prescription (adjusted HR were 0.99[95%CI 0.96-1.03], 1.04[95%CI 0.99-1.09], 1.07[95%CI 1.00-1.14]). CONCLUSION: PPV23 vaccination in older adults may result in a small reduction in the incidence of total ARI presentations in primary care. However, the effect is small and residual confounding cannot be excluded.

Treatment outcomes amongst older people with HIV infection receiving antiretroviral therapy.

OBJECTIVES: There is conflicting data regarding the response of older people with HIV (PWH) to antiretroviral therapy (ART). The objective of this study was to evaluate the long-term immunological and virological responses, changes in regimen, and adverse drug reactions (ADRs) in older participants (50+ years) compared with younger (18-34 years) and middle-aged (35-49 years) PWH. METHODS: A retrospective review of medical records was conducted on 1622 participants who received ART in Yunnan Province, China, from 2010 to 2019. The study compared CD4+ T-cell counts, CD4+/CD8+ ratio, and relative numbers between different groups using the Kruskal-Wallis test. Cox proportional hazards regression models were used to identify variables associated with the occurrence of immune reconstitution insufficiency. The rates of immune reconstitution, incidence of ADRs, and rates of treatment change were analyzed using the chi-squared test or Fisher's exact test. RESULTS: Over 95% achieved viral load 200 copies/ml or less, with no age-related difference. However, older participants exhibited significantly lower CD4+ T-cell counts and CD4+/CD8+ recovery post-ART (P < 0.001), with only 32.21% achieving immune reconstitution (compared with young: 52.16%, middle-aged: 39.29%, P < 0.001) at the end of follow-up. Middle-aged and elderly participants changed ART regimens more because of ADRs, especially bone marrow suppression and renal dysfunction. CONCLUSION: Although the virological response was consistent across age groups, older individuals showed poorer immune responses and higher susceptibility to side effects. This underscores the need for tailored interventions and comprehensive management for older patients with HIV.

Coverage and predictors of influenza and pertussis vaccination during pregnancy: a whole of population-based study.

BACKGROUND: Respiratory infections including influenza and pertussis are associated with significant morbidity and mortality in mothers and newborns. Vaccination during pregnancy against influenza and pertussis is recommended for all women but data on uptake in Australia is limited. METHODS: We conducted a retrospective population-based cohort study in Australia's largest state, New South Wales (NSW), using a Perinatal Data Collection (PDC). Data included demographic, pregnancy, and birth details including pertussis and influenza vaccination during pregnancy for all women giving birth between 01 January 2016 and 31 December 2020. We used descriptive statistics to assess uptake of influenza and pertussis vaccination during pregnancy and Poisson loglinear regression to estimate associations between maternal characteristics and vaccine receipt. RESULTS: During 2016-2020, there were 477,776 births (mean maternal age 32.25 years). In 176,255 (36.9%) births the mother received both vaccines; 202,922 (42.5%) influenza and 315,620 (66.1%) pertussis vaccine. From 2016 to 2020, reported coverage increased from 26.7% to 58.7% for influenza and 43.1% to 78.8% for pertussis, respectively. After adjustment, characteristics associated with lower likelihood of receiving influenza and pertussis vaccination included: younger age (<30 years), being born in Australia/New Zealand, from lower socio-economic strata, having previous pregnancies, being later to first antenatal care, utilising the public hospital care model, smoking, having chronic hypertension and BMI > 25 kg/m2. CONCLUSIONS: While reported coverage of both influenza and pertussis vaccine in birthing women in NSW has increased over time, disparities in coverage exist and they highlight areas where evidence-based interventions to improve maternal vaccination could be targeted.

Association between proton pump inhibitor use and neurological or psychiatric disorders: a systematic review protocol.

OBJECTIVE: The objective of this review is to examine the association between proton pump inhibitors (PPIs) and neurological and/or psychiatric disorders in adults. INTRODUCTION: The association between PPIs and neurological and/or psychiatric disorders remains unclear, despite the widespread use of the medications. A systematic review is required to investigate the risk of developing neurological and/or psychiatric disorders following the use of PPIs. INCLUSION CRITERIA: Studies including participants aged ≥18 years and using any PPIs, including participants with comorbid conditions or using other medications, will be considered for inclusion. Randomized controlled trials, quasi-experimental studies, and observational studies examining the association of neurological and/or psychiatric disorders with the use of PPIs among adults will be included. METHODS: MEDLINE, Embase, PsycINFO, CINAHL, and Cochrane CENTRAL databases will be searched from inception until the present. Two authors will independently screen and review the titles, abstracts, and full texts. The methodological quality of included studies will be assessed using the JBI critical appraisal checklists. Study characteristics, populations, type and duration of PPI usage, status of existing neurological and/or psychiatric disorders, comorbidity conditions, use of other medications, identification of neurological and/or psychiatric disorders (International Classification of Diseases codes vs others), and estimation of the associated neurological and/or psychiatric disorders will be extracted. Studies will be pooled using statistical meta-analysis where available; otherwise, the findings will be presented in narrative format. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach for grading the certainty of evidence will be followed. REVIEW REGISTRATION: PROSPERO CRD42022355543.

Comparative genomics reveals the hybrid origin of a macaque group.

Although species can arise through hybridization, compelling evidence for hybrid speciation has been reported only rarely in animals. Here, we present phylogenomic analyses on genomes from 12 macaque species and show that the fascicularis group originated from an ancient hybridization between the sinica and silenus groups ~3.45 to 3.56 million years ago. The X chromosomes and low-recombination regions exhibited equal contributions from each parental lineage, suggesting that they were less affected by subsequent backcrossing and hence could have played an important role in maintaining hybrid integrity. We identified many reproduction-associated genes that could have contributed to the development of the mixed sexual phenotypes characteristic of the fascicularis group. The phylogeny within the silenus group was also resolved, and functional experimentation confirmed that all extant Western silenus species are susceptible to HIV-1 infection. Our study provides novel insights into macaque evolution and reveals a hybrid speciation event that has occurred only very rarely in primates.

Genomic Evidence for the Nonpathogenic State in HIV-1-Infected Northern Pig-Tailed Macaques.

HIV-1 is a highly host-specific retrovirus that infects humans but not most nonhuman primates. Thus, the lack of a suitable primate model that can be directly infected with HIV-1 hinders HIV-1/AIDS research. In the previous study, we have found that the northern pig-tailed macaques (NPMs) are susceptible to HIV-1 infection but show a nonpathogenic state. In this study, to understand this macaque-HIV-1 interaction, we assembled a de novo genome and longitudinal transcriptome for this species during the course of HIV-1 infection. Using comparative genomic analysis, a positively selected gene, Toll-like receptor 8, was identified with a weak ability to induce an inflammatory response in this macaque. In addition, an interferon-stimulated gene, interferon alpha inducible protein 27, was upregulated in acute HIV-1 infection and acquired an enhanced ability to inhibit HIV-1 replication compared with its human ortholog. These findings coincide with the observation of persistently downregulated immune activation and low viral replication and can partially explain the AIDS-free state in this macaque following HIV-1 infection. This study identified a number of unexplored host genes that may hamper HIV-1 replication and pathogenicity in NPMs and provided new insights into the host defense mechanisms in cross-species infection of HIV-1. This work will facilitate the adoption of NPM as a feasible animal model for HIV-1/AIDS research.

Longitudinal analysis of immunocyte responses and inflammatory cytokine profiles in SFTSV-infected rhesus macaques.

Severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging bunyavirus, causes severe fever with thrombocytopenia syndrome (SFTS), with a high fatality rate of 20%-30%. At present, however, the pathogenesis of SFTSV remains largely unclear and no specific therapeutics or vaccines against its infection are currently available. Therefore, animal models that can faithfully recapitulate human disease are important to help understand and treat SFTSV infection. Here, we infected seven Chinese rhesus macaques (Macaca mulatta) with SFTSV. Virological and immunological changes were monitored over 28 days post-infection. Results showed that mild symptoms appeared in the macaques, including slight fever, thrombocytopenia, leukocytopenia, increased aspartate aminotransferase (AST) and creatine kinase (CK) in the blood. Viral replication was persistently detectable in lymphoid tissues and bone marrow even after viremia disappeared. Immunocyte detection showed that the number of T cells (mainly CD8+ T cells), B cells, natural killer (NK) cells, and monocytes decreased during infection. In detail, effector memory CD8+ T cells declined but showed increased activation, while both the number and activation of effector memory CD4+ T cells increased significantly. Furthermore, activated memory B cells decreased, while CD80+/CD86+ B cells and resting memory B cells (CD27+CD21+) increased significantly. Intermediate monocytes (CD14+CD16+) increased, while myeloid dendritic cells (mDCs) rather than plasmacytoid dendritic cells (pDCs) markedly declined during early infection. Cytokines, including interleukin-6 (IL-6), interferon-inducible protein-10 (IP-10), and macrophage inflammatory protein 1 (MCP-1), were substantially elevated in blood and were correlated with activated CD4+ T cells, B cells, CD16+CD56+ NK cells, CD14+CD16+ monocytes during infection. Thus, this study demonstrates that Chinese rhesus macaques infected with SFTSV resemble mild clinical symptoms of human SFTS and provides detailed virological and immunological parameters in macaques for understanding the pathogenesis of SFTSV infection.

Examination of validity of identifying congenital heart disease from hospital discharge data without a gold standard: Using a data linkage approach.

BACKGROUND: Administrative health data has been used extensively to examine congenital heart disease (CHD). However, the accuracy and completeness of these data must be assessed. OBJECTIVES: To use data linkage of multiple administrative data sources to examine the validity of identifying CHD cases recorded in hospital discharge data. METHODS: We identified all liveborn infants born 2013-2017 in New South Wales, Australia with a CHD diagnosis up to age one, recorded in hospital discharge data. Using record linkage to multiple data sources, the diagnosis of CHD was compared with five reference standards: (i) multiple hospital admissions containing CHD diagnosis; (ii) receiving a cardiac procedure; (iii) CHD diagnosis in the Register of Congenital Conditions; (iv) cardiac-related outpatient health service recorded; and/or (v) cardiac-related cause of death. Positive predictive values (PPV) comparing CHD diagnosis with the reference standards were estimated by CHD severity and for specific phenotypes. RESULTS: Of 485,239 liveborn infants, there were 4043 infants with a CHD diagnosis identified in hospital discharge data (8.3 per 1000 live births). The PPV for any CHD identified in any of the five methods was 62.8% (95% confidence interval [CI] 60.9, 64.8), with PPV higher for severe CHD at 94.1% (95% CI 88.2, 100). Infant characteristics associated with higher PPVs included lower birthweight, presence of a syndrome or non-cardiac congenital anomaly, born to mothers aged <20 years and residing in disadvantaged areas. CONCLUSION: Using data linkage of multiple datasets is a novel and cost-effective method to examine the validity of CHD diagnoses recorded in one dataset. These results can be incorporated into bias analyses in future studies of CHD.

Associations between severe and notifiable respiratory infections during the first trimester of pregnancy and congenital anomalies at birth: a register-based cohort study.

BACKGROUND: Evidence regarding the association between acute respiratory infections during pregnancy and congenital anomalies in babies, is limited and conflicting. The aim of this study was to examine the association between acute respiratory infections during the first trimester of pregnancy and congenital anomalies in babies using record linkage. METHODS: We linked a perinatal register to hospitalisation and disease notifications in the Australian state of New South Wales (NSW) between 2001 to 2016. We quantified the risk of congenital anomalies, identified from the babies' linked hospital record in relation to notifiable respiratory and other infections during pregnancy using generalized Estimating Equations (GEE) adjusted for maternal sociodemographic and other characteristics. RESULTS: Of 1,453,037 birth records identified from the perinatal register between 2001 and 2016, 11,710 (0.81%) mothers were hospitalised for acute respiratory infection, 2850 (0.20%) had influenza and 1011 (0.07%) had high risk infections (a record of cytomegalovirus, rubella, herpes simplex, herpes zoster, toxoplasmosis, syphilis, chickenpox (varicella) and zika) during the pregnancy. During the first trimester, acute respiratory infection, influenza and high-risk infections were reported by 1547 (0.11%), 399 (0.03%) and 129 (0.01%) mothers. There were 15,644 (1.08%) babies reported with major congenital anomalies, 2242 (0.15%) with cleft lip/ plate, 7770 (0.53%) with all major cardiovascular anomalies and 1746 (0.12%) with selected major cardiovascular anomalies. The rate of selected major cardiovascular anomalies was significantly higher if the mother had an acute respiratory infection during the first trimester of pregnancy (AOR 3.64, 95% CI 1.73 to 7.66). The rates of all major congenital anomalies and all major cardiovascular anomalies were also higher if the mother had an acute respiratory infection during the first trimester of pregnancy, however the difference was no statistically significant. Influenza during the first trimester was not associated with major congenital anomalies, selected major cardiovascular anomalies or all major cardiovascular anomalies in this study. CONCLUSION: This large population-based study found severe acute respiratory infection in first trimester of pregnancy was associated with a higher risk of selected major cardiovascular anomalies in babies. These findings support measures to prevent acute respiratory infections in pregnant women including through vaccination.

A Novel Vpu Adaptive Mutation of HIV-1 Degrades Tetherin in Northern Pig-Tailed Macaques (Macaca leonina) Mainly via the Ubiquitin-Proteasome Pathway and Increases Viral Release.

Tetherin prevents viral cross-species transmission by inhibiting the release of multiple enveloped viruses from infected cells. With the evolution of simian immunodeficiency virus of chimpanzees (SIVcpz), a pandemic human immunodeficiency virus type 1 (HIV-1) precursor, its Vpu protein can antagonize human tetherin (hTetherin). Macaca leonina (northern pig-tailed macaque [NPM]) is susceptible to HIV-1, but host-specific restriction factors limit virus replication in vivo. In this study, we isolated the virus from NPMs infected with strain stHIV-1sv (with a macaque-adapted HIV-1 env gene from simian-human immunodeficiency virus SHIV-KB9, a vif gene replaced by SIVmac239, and other genes originating from HIV-1NL4.3) and found that a single acidic amino acid substitution (G53D) in Vpu could increase its ability to degrade the tetherin of macaques (mTetherin) mainly through the proteasome pathway, resulting in an enhanced release and resistance to interferon inhibition of the mutant stHIV-1sv strain, with no influence on the other functions of Vpu. IMPORTANCE HIV-1 has obvious host specificity, which has greatly hindered the construction of animal models and severely restricted the development of HIV-1 vaccines and drugs. To overcome this barrier, we attempted to isolate the virus from NPMs infected with stHIV-1sv, search for a strain with an adaptive mutation in NPMs, and develop a more appropriate nonhuman primate model of HIV-1. This is the first report identifying HIV-1 adaptations in NPMs. It suggests that while tetherin may limit HIV-1 cross-species transmission, the Vpu protein in HIV-1 can overcome this species barrier through adaptive mutation, increasing viral replication in the new host. This finding will be beneficial to building an appropriate animal model for HIV-1 infection and promoting the development of HIV-1 vaccines and drugs.

Effectiveness of quadrivalent HPV vaccination in reducing vaccine-type and nonvaccine-type high risk HPV infection.

This study aimed to assess human papillomavirus (HPV) vaccine effectiveness (VE) against both vaccine-type and nonvaccine-type high-risk HPV (hrHPV) infection, and duration of protection in United States. The study population was female participants aged 18-35 years with an HPV vaccination history and genital testing for HPV from the National Health and Nutrition Examination Survey, 2007-2016. Participants vaccinated before sexual debut were assessed against 13 nonvaccine-type hrHPV infection including 31/33/35/39/45/51/52/56/58/59/68/73/82. Multivariable logistic regression was used to estimate VE overall, by age at diagnosis, time since vaccination and lifetime sexual partners. A total of 3866 women were included in the analysis, with 23.3% (95% CI 21.3%-25.4%) having been vaccinated (≥1 dose). VE against vaccine-type HPV18/16/11/6 infection was 58% overall, which was mainly driven by those aged 18-22 years (VE = 64%) and 23-27 years (65%). Among participants aged 18-22 years vaccinated before sexual debut, the VE was 47% (23%-64%) against 13 nonvaccine-type hrHPV and 61% (95% CI 36%-77%) against 5 selected nonvaccine-type hrHPV35/39/52/58/59. Both direct effectiveness and cross-protection maintained effective for 5-10 years post vaccination. We also found the prevalence of ever diagnosed cervical cancer among vaccinated was significantly lower (0.46%, 4/874) than that among unvaccinated participants (1.27%, 38/2992). These findings highlight the potential of significant reduction of cervical cancer following the universal HPV vaccination programme.

After-hours consultations and antibiotic prescribing for self-limiting upper respiratory tract infections in primary-care practices.

OBJECTIVES: To determine the association between after-hours consultations and the likelihood of antibiotic prescribing for self-limiting upper respiratory tract infections (URTIs) in primary care practices. DESIGN: A cross-sectional analysis using Australian national primary-care practice data (MedicineInsight) between February 1, 2016 and January 31, 2019. SETTING: Nationwide primary-care practices across Australia. PARTICIPANTS: Adult and pediatric patients who visited primary care practices for first-time URTIs. METHODS: We estimated the proportion of first-time URTI episodes for which antibiotic prescribing occurred on the same day (immediate prescribing) using diagnoses and prescription records in the electronic primary-care database. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the likelihood of antibiotic prescribing by the time of primary care visits were calculated using generalized estimating equations. RESULTS: Among 357,287 URTI episodes, antibiotics were prescribed in 172,605 episodes (48.3%). After adjusting for patients' demographics, practice characteristics, and seasons, we detected a higher likelihood of antibiotic prescribing on weekends compared to weekdays (OR, 1.42; 95% CI, 1.39-1.45) and on national public holidays compared to nonholidays (OR, 1.23; 95% CI, 1.17-1.29). When we controlled for patient presentation and diagnosis, the association between antibiotic prescribing and after-hours consultations remained significant: weekend versus weekdays (OR, 1.37; 95% CI, 1.33-1.41) and holidays versus nonholidays (OR, 1.10; 95% CI, 1.03-1.18). CONCLUSIONS: Primary-care consultations on weekends and public holidays were associated with a higher likelihood of immediate antibiotic prescribing for self-limiting URTIs in primary care. This finding might be attributed to lower resourcing in after-hours health care.

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Litter decomposition is one of the most important ecosystem processes, which plays a critical role in regu-lating nutrient cycling and energy flow in terrestrial ecosystems. The influence of litter inputs on soil microbial community is helpful for understanding the relationship between soil microbial diversity and terrestrial ecosystem function. We conducted a meta-analysis to examine how litter inputs affect soil microbial activity (fungi, bacteria, actinomycetes) and microbial biomass carbon, nitrogen in China. The results showed that compared with non-litter input, soil microbial biomass carbon and nitrogen were significantly increased by 3.9% and 4.4% respectively after litter inputs. Soil fungal PLFA, bacterial PLFA, and total microbial PLFA were increased by 4.0%, 3.1% and 2.4%, respectively. The effects of litter inputs differed significantly with climatic region, annual precipitation, vege-tation type, and soil pH. Under different climate conditions, the responses of soil microbe showed the trend of subtropical monsoon climatic region > temperate monsoon climatic region > temperate continental climatic region, which increased first and then decreased with increasing annual precipitation. Under different vegetation types, the responses of soil microbes showed the trend of broad-leaved forest > grassland ≈ mixed forest > coniferous forest.

A variant-proof SARS-CoV-2 vaccine targeting HR1 domain in S2 subunit of spike protein.

The emerging SARS-CoV-2 variants, commonly with many mutations in S1 subunit of spike (S) protein are weakening the efficacy of the current vaccines and antibody therapeutics. This calls for the variant-proof SARS-CoV-2 vaccines targeting the more conserved regions in S protein. Here, we designed a recombinant subunit vaccine, HR121, targeting the conserved HR1 domain in S2 subunit of S protein. HR121 consisting of HR1-linker1-HR2-linker2-HR1, is conformationally and functionally analogous to the HR1 domain present in the fusion intermediate conformation of S2 subunit. Immunization with HR121 in rabbits and rhesus macaques elicited highly potent cross-neutralizing antibodies against SARS-CoV-2 and its variants, particularly Omicron sublineages. Vaccination with HR121 achieved near-full protections against prototype SARS-CoV-2 infection in hACE2 transgenic mice, Syrian golden hamsters and rhesus macaques, and effective protection against Omicron BA.2 infection in Syrian golden hamsters. This study demonstrates that HR121 is a promising candidate of variant-proof SARS-CoV-2 vaccine with a novel conserved target in the S2 subunit for application against current and future SARS-CoV-2 variants.

Effectiveness of influenza vaccination in reducing influenza-like illness and related antibiotic prescriptions in adults from a primary care-based case-control study.

BACKGROUND: Evidence on the effectiveness of influenza vaccine in preventing antibiotic prescriptions for influenza-like illness (ILI) in adults is limited. METHODS: A primary care-based case-control study was conducted to estimate influenza vaccine effectiveness (VE) against influenza-like illness (ILI) and antibiotic prescribing for ILI in adults aged ≥40 years. Cases were patients diagnosed with ILI from 1st June to 30th September in each year, 2015-2018; a subset of those with ILI prescribed antibiotics was also defined. Controls were patients attending a practice who did not receive an ILI diagnosis. Generalised estimating equations were used to calculate adjusted VE overall, by age (<65 versus ≥65 years) and comorbidity status. RESULTS: The number of ILI cases varied from 558 in 2018 to 2901 in 2017 and controls from 86618 in 2015 to 136763 in 2017. Over 4 years the pooled estimate of VE was 24% (95%CI, 11% to 34%) against ILI and 15% (95%CI, -3% to 29%) against antibiotic prescription for ILI. Influenza vaccine was effective in reducing ILI with an associated antibiotic prescriptions in patients aged <65 years (VE=23%, 95%CI, 3% to 38%) and if no comorbidities were recorded (VE=22%, 95%CI, 1% to 39%) but not in other subgroups. CONCLUSIONS: Influenza vaccine reduced the likelihood of antibiotic prescriptions for ILI in low-risk adults (40-64 years and those without comorbidities).

Comparison of primary liver cancer mortality estimates from World Health Organization, global burden disease and global cancer observatory.

AIMS: This study aims to compare estimates of primary liver cancer mortality from World Health Organization (WHO), Global Burden Disease (GBD) and Global Cancer Observatory (GCO). METHODS: Liver cancer mortality was extracted from WHO, GBD and GCO for 92 countries for the most recent year. Age-standardized rate (ASR) was computed and used for current comparisons across the three data sources. Temporal trend for 75 countries was analysed and compared between WHO and GBD from 1990 to 2019 using joinpoint regression. Average annual percentage change for the most recent 10 years was used as indicator for change. RESULTS: The estimates of ASR were quite consistent across the three data sources, but most similar estimates were found between WHO and GCO in both region and country levels. The differences in ASR were negatively correlated with completeness of cause-of-death registration, human development index and proportion of liver cancer because of alcohol consumption. Consistent trends of ASR were found from 35 countries between WHO and GBD in the most recent 10 years. However, opposite trends were found from 10 countries with five from Southern America, four from Europe and one from Asia. Of the 18 countries for projection, opposite trends between WHO and GBD were found from seven countries. CONCLUSION: While the ASR of primary liver cancer mortality was comparable across the three data sources, most similar estimates were found between WHO and GCO. The opposite trends found from 10 countries between WHO and GBD raised concerns of true patterns in these countries.

HIV-1 but not SIVmac239 induces higher interferon-α antiviral state in chronic infected northern pig-tailed macaques (Macaca leonina).

Studies have shown that interferon (IFN)-α has an inhibitory effect on human immunodeficiency virus type 1 (HIV-1) replication in the acute infection stage, but its role in chronic infection is still unclear. We previously established a nonpathogenic HIV-1 and pathogenic simian immunodeficiency virus (SIV) model in northern pig-tailed macaques (NPMs, Macaca leonina). In the current study, we detected viral RNA and DNA in various tissues (axillary lymph nodes (LNs), inguinal LNs, and spleen) in HIV-1NL4-3- and SIVmac239-infected NPM during the chronic stage of infection. Results indicated that the levels of viral DNA and RNA were higher in the tested tissues (LNs and spleen) of the SIVmac239-infected NPMs than in the HIV-1NL4-3 infected NPMs. Furthermore, IFN-α expression was higher in the HIV-infected tissues than in the SIV-infected controls. The HIV restriction factors induced by IFN-α (i.e., tetherin and MX2), as well as inflammatory factors IFN-γ, tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6), were analyzed using real-time polymerase chain reaction (PCR) and immunofluorescence staining assays. Results showed that their expression levels were much higher in the HIV-infected tissues than in the SIV-infected controls. These findings were confirmed by in vitro experiments on healthy NPM peripheral blood mononuclear cells infected with HIV-1NL4-3, which showed lower viral replication, higher IFN-α expression, and an antiviral status. This study demonstrated that HIV-1 infection, but not SIVmac239 infection, in NPMs caused higher expression of IFN-α and induced a higher antiviral status. This may be one of the reasons why HIV-1 cannot replicate at a high level or develop into AIDS in NPMs.

The impact of hepatitis B vaccination in the United States, 1999-2018.

BACKGROUND AND AIMS: Hepatitis B vaccine has been included in the infant immunization schedule since 1991 in the United States. We aimed to assess its effectiveness against HBV infection and its impact on mortality. APPROACH AND RESULTS: The study population was participants aged 6+ years with an HBV vaccination history and an HBV serologic test from the National Health and Nutrition Examination Survey, 1999-2018. Participants aged 18+ years with linked mortality records from 1999-2014 were followed for mortality analysis. Multivariable logistic regression was used to compute vaccine effectiveness (VE) overall, by year of birth, and by age. Cox regression was used to estimate HRs for all-cause, cancer-related, and cardiovascular disease-related mortality. A total of 64,107 participants were included in the main analysis, with 29,600 (40.7%) having completed HBV vaccination (three or more doses, vaccinated). The highest vaccination uptake was found among those born after 1991, at 86.5%. Vaccinated participants had higher prevalence of vaccine-induced immunity than the unvaccinated (47.2% vs. 7.4%). Among those born after 1991, VE was found at 58% (95% CI, 18%-79%) overall and 85% for those aged ≥20 years (mean age, 22), whereas no effect was found among those born prior to 1990. HBV vaccination was associated with reduced risk of all-cause mortality (HR, 0.78; 95% CI, 0.68-0.90) and cancer-related mortality (HR, 0.76; 95% CI, 0.58-1.00) but not for cardiovascular disease-related mortality. CONCLUSIONS: In the universal infant vaccination era, the HBV vaccine has shown substantial effectiveness against HBV infection and maintained strong protection for 20 years. It was also associated with reduced risk of all-cause and cancer-related mortality.