Universal Vaccination Program Research Articles

HBV 2021: New therapeutic strategies against an old foe.

Hepatitis B virus (HBV) affects more than 250 million people worldwide, and is one of the major aetiologies for the development of cirrhosis and hepatocellular carcinoma (HCC). In spite of universal vaccination programs, HBV infection is still a public health problem, and the limited number of available therapeutic approaches complicates the clinical management of these patients. Thus, HBV infection remains an unmet medical need that requires a continuous effort to develop new individual molecules, treatment combinations and even completely novel therapeutic strategies to achieve the goal of HBV elimination. The following review provides an overview of the current situation in chronic HBV infection, with an analysis of the scientific rationale of certain clinical interventions and, more importantly, explores the most recent developments in the field of HBV drug discovery.

Effect of the varicella vaccination implementation on the development of herpes zoster in children and adolescents.

Herpes zoster (HZ) is an infectious disease caused by latent varicella-zoster virus reactivation. There are conflicting reports on the varicella vaccine's effect on the incidence of HZ in children and adolescents. This study aimed to determine the impact of the single dose of varicella vaccination on HZ prevalence during childhood and adolescence. The study included children and adolescents aged <18 years who presented to the dermatology outpatient clinic between 2005 and 2019 and were diagnosed with HZ. Considering that the universal vaccination program started to be implemented in Turkey in 2013, non-vaccinated cases in the prevaccination period, vaccinated cases in the postvaccination period, and non-vaccinated patients in the postvaccination period were compared in terms of HZ prevalence and demographic features. After the initiation of the varicella vaccination program, the prevalence of HZ was found to decrease by 24.7% in all. The HZ prevalence was significantly reduced in vaccinated children, while the rate of decrease in non-vaccinated children was low (58.6% and 16.4%, respectively). The median age of the non-vaccinated cases in the postvaccination period (10 [min 0.5-max 17] years) was significantly higher compared to the other groups (p < 0.001). The number of cases aged <2 years was the highest in the vaccinated group (p < 0.001). Administration of a single dose of varicella vaccine was insufficient to decrease the prevalence of HZ <18 years of age. In the post-vaccination period, the frequency of HZ in unvaccinated cases increased in adolescence. In vaccinated children, HZ seems to develop at an earlier age.

Hepatitis B virus infection among pregnant mothers and children after the introduction of the universal vaccination program in Central Vietnam

A birth cohort study was conducted in Khan Hoa Province, central Vietnam between 2009 and 2012 to determine the seroprevalence of hepatitis B virus (HBV) in pregnant women and their children, and associated risk factors. We enrolled 1987 pregnant women with their babies at the birth phase, and 12.6% (95% confidence interval [CI]: 11.1–14.0) of mothers were hepatitis B surface antigen (HBsAg)+. At 2-year follow-up phase, 1339 (67.4%) children were enrolled of whom 76.6% completed hepatitis B vaccines (HepB) and 1.9% (95% CI: 1.2–2.7) were HBsAg+. When mothers were hepatitis B e antigen (HBeAg)+, 28.3% of children have got infected even with complete HepB. HBV infection in mothers, hepatitis B surface antibody (anti-HBs antibody) below the seroprotective level in children, and mothers with pre-pregnancy low body mass index were associated with HBV infection in children. Meanwhile, HBV infection in children, older maternal age, no or incomplete doses of HepB, and boys were associated with anti-HBs antibody below the seroprotective level in children. Our birth cohort study determined a low rate of congenital HBV infection and associated risk factors in Vietnam, however further studies are needed to advance prevention including anti-viral therapy in pregnant women at high risk.

Development and implementation of a potential coronavirus disease 2019 (COVID-19) vaccine: A systematic review and meta-analysis of vaccine clinical trials.

BackgroundTo date, there is no comprehensive systematic review and meta-analysis to assess the suitability of COVID-19 vaccines for mass immunization. The current systematic review and meta-analysis was conducted to evaluate the safety and immunogenicity of novel COVID-19 vaccine candidates under clinical trial evaluation and present a contemporary update on the development and implementation of a potential vaccines.MethodsFor this study PubMed, MEDLINE, and Embase electronic databases were used to search for eligible studies on the interface between novel coronavirus and vaccine design until December 31, 2020.ResultsWe have included fourteen non-randomized and randomized controlled phase I-III trials. Implementation of a universal vaccination program with proven safety and efficacy through robust clinical evaluation is the long-term goal for preventing COVID-19. The immunization program must be cost-effective for mass production and accessibility. Despite pioneering techniques for the fast-track development of the vaccine in the current global emergency, mass production and availability of an effective COVID-19 vaccine could take some more time.ConclusionOur findings suggest a revisiting of the reported solicited and unsolicited systemic adverse events for COVID-19 candidate vaccines. Hence, it is alarming to judiciously expose thousands of participants to COVID-19 candidate vaccines at Phase-3 trials that have adverse events and insufficient evidence on safety and effectiveness that necessitates further justification.

Effectiveness of a universal vaccination program with an HPV quadrivalent vaccine in young Brazilian women

We examined human papillomavirus (HPV) vaccine effectiveness in a nationwide sample of women aged 16 to 25 years who utilized the public health system in Brazil. This was a cross-sectional, multicentric survey conducted between September 2016 and November 2017 (POP-Brazil Study). A total of 5,945 young adult women were recruited from 119 public primary care units from all 27 federative units of Brazil by trained health professionals. The participants participated in a face-to-face interview and provided biological samples for genital HPV analysis. HPV genotyping was performed using a Linear Array HPV genotyping test in a central laboratory. Sampling weights were applied to the data. Overall, 11.92% (95% CI 10.65, 13.20) of the participants reported having been vaccinated. The frequency of vaccination was highest in 16- to 17-year-old women, with a decreasing vaccination rate with increasing age, and vaccinated women were more likely to belong to the high socioeconomic status group. The use of a quadrivalent vaccine decreased the HPV types 6, 11, 16, and 18 by 56.78%, from 15.64% in unvaccinated women to 6.76% in vaccinated women (P < 0.01), even after adjustment for age. Those who received the vaccine had lower HPV 16 (2.34% in vaccinated vs 8.91% in unvaccinated, P < 0.01) and 6 rates (2.06% vs 5.77%, P < 0.01). Additionally, a higher rate of high-risk HPV types other than HPV 16 and 18 (40.47% in vaccinated vs 32.63% in unvaccinated, P < 0.01) was observed. In conclusion, the results of this study support the effectiveness of HPV vaccination in Brazil. Continuous surveillance must be assured to monitor the HPV infection rate in the vaccination era.

Serologic evidence of the circulation of the hepatitis E virus and the prevalence of antibodies against hepatitis A in an indigenous population in northern Argentina

In 2005 a universal vaccination program against hepatitis A was introduced in Argentina. Nevertheless, there are still some unvaccinated marginal population groups. There are no data about the seroprevalence of hepatitis E in the northern region of Argentina mainly because of lack of awareness of this emergent pathogen. We aimed to determine the seroprevalence of hepatitis A, and hepatitis E in an indigenous population in northern Argentina. One hundred and twenty six (126) donor serum samples collected near San Salvador de Jujuy were analyzed for anti-HAV IgG and HEV IgG and IgM, alkaline phosphatase and transaminase values. Volunteers were interviewed about their living conditions, animal farming, consumption of tap water or river water, and level of education. Seroprevalence of specific anti-HAV antibodies was high (80.2%, 95% confidence interval, 72.1–86.7%) in children under 5 years of age, indicating early infection in life. Seroprevalence of anti-HEV antibodies was 5.6% (95% CI: 2.3–11.2%), being slightly higher than the values found in healthy patients from other regions of the country. Although we could not characterize the genotype of the circulating HEV strain, the clear epidemiological difference between seroprevalence of HAV and HEV in a community with poor sanitary conditions suggest that the circulating HEV strains spread through a different transmission route than HAV. Furthermore a significant correlation between anti-HEV IgG and swine farming was found (p<0.05), which supports a zoonotic transmission path. We reassessed the epidemiological pattern of HAV infection and reported evidence of HEV infection for the first-time in a community belonging to the Guarani ethnic group, highlighting the need to include hepatitis E testing in routine diagnostics in the region.

Acceptance of universal varicella vaccination among Swiss pediatricians and general practitioners who treat pediatric patients

BackgroundOver the last two decades, several countries have initiated universal varicella vaccination (UVV) programs in infants. In 2019, the Swiss National Immunization Technical Advisory Group (NITAG) decided to start evaluating the introduction of universal varicella vaccination. There is a theoretical concern that suboptimal vaccination coverage could lead to a shift in the varicella incidence to older age groups, thereby potentially increasing complication rates. To achieve a high vaccination coverage rate, it is important that practicing physicians comply with a potential recommendation for UVV.We studied the perception of varicella and the current vaccination behavior among Swiss pediatricians and general practitioners (GPs) who treat children. We also assessed their intention to advise parents to vaccinate their children against varicella in the event the Swiss NITAG will recommend UVV.MethodsPrimary data was collected through a structured, 20-min online survey with Swiss pediatricians and GPs who treat children.Results150 physicians participated in the study: 40 GPs in the German-speaking part, 20 GPs in the French-speaking part, 67 pediatricians in the German-speaking part, and 23 pediatricians in the French-speaking part.The majority (64%) of all participants reported that they currently recommend varicella vaccination for risk groups according to the national immunization plan. About one third of physicians (35%) – predominantly pediatricians – currently already recommend it for all infants. In these situations, a measles, mumps, rubella, varicella combination vaccine is currently used by 58% for the first dose and by 59% for the second dose.86% of participants stated that they would advise parents to have their children vaccinated against varicella in case of a recommendation for UVV by the Swiss NITAG. 68% responded that they expect many questions from parents and 65% agreed that they have good arguments to convey the importance of varicella vaccination.ConclusionsThe survey study results show that most participating pediatricians and GPs indicated a favorable attitude towards childhood vaccination against varicella in the setting of a Swiss NITAG recommendation for UVV. This data shows the importance of NITAG recommendations in influencing vaccine education and supporting achievement of high coverage of varicella vaccination.

Hepatocellular carcinoma in transfusion dependent thalassemia patients: a review from a clinical perspective

Survival in patients with transfusion-dependent thalassemias (TDT) has increased, and complications such as hepatocellular carcinoma (HCC) are emerging. Risk factors include viral infection, mainly hepatitis C virus (HCV), iron overload, the presence of cirrhosis, and immune dysregulation. Median survival after HCC occurrence has been estimated at 12 months, while data regarding the incidence of HCC in this population are minimal. Implementing effective hepatitis B virus (HBV)/HCV antiviral treatment and universal HBV vaccination programs is expected to decrease the risk for hepatocarcinogenesis substantially. Significant hemosiderosis and hepatic fibrosis are common in patients with TDT despite chelation therapy and have been correlated with HCC development. Thus, iron overload should be monitored with liver iron concentration and ferritin levels, and effective chelation therapy should be applied. In addition, all TDT patients, particularly those with cirrhosis, should be under surveillance every six months with abdominal ultrasound ± alpha-fetoprotein levels, as this combination seems to provide better sensitivity for early HCC detection.

An exploratory study of undergraduate healthcare student perspectives regarding human papillomavirus and vaccine intent in India.

Objective:Safe and effective human papillomavirus vaccines are available against cervical cancer and other human papillomavirus–associated diseases. Vaccine uptake is low in India given lack of universal vaccination programme. This exploratory study describes the medical, dental and nursing undergraduate student perspectives about human papillomavirus and intentions to receive the vaccine.Methods:Using a cross-sectional, explorative study design, we conducted two focus group discussions among a convenience sample of male (n = 11) and female (n = 9) student group aged ⩾18 years, respectively, at a medical college in South India. The focus group discussion sessions were recorded, transcribed and analysed using thematic content analysis.Results:Over half of the students showed adequate knowledge of cervical cancer and human papillomavirus. Medical students had much in-depth knowledge of cervical cancer, vaccine cost and its side effects compared to dental and nursing students. Human papillomavirus vaccine knowledge was relatively less among males compared to females; most male participants were unaware of the availability of the human papillomavirus vaccine. Intention to receive the vaccine was higher among females than males. All the participants had positive attitude in creating awareness in the community and making the vaccine cost-effective. Cultural concerns and high vaccine cost were cited major barriers for vaccine uptake. Suggestion of physician recommendation in promotion of human papillomavirus vaccine uptake was an emerging theme.Conclusion:Educating male students and those enrolled in dental and nursing courses about human papillomavirus vaccine, addressing cultural concerns and advocating provider recommendation for promoting vaccine uptake are potential strategies to improve future human papillomavirus vaccine intent among students and recommendations to patients in their role as future healthcare provider.

34. Impact of Universal Mass Vaccination Programs of Children Against Hepatitis a with 2-dose and 1-dose Schedules: A Systematic Literature Review

BackgroundWith more than 100 million new hepatitis A (HepA) virus (HAV) infections estimated each year, HepA is a serious health concern worldwide. Several countries implemented 2- or 1-dose universal mass vaccination (UMV) programs of children with HAV vaccines. Here we present the first systematic review describing the impact of 2- and 1-dose UMV programs on HepA incidence and related health outcomes.MethodsWe systematically searched several databases for data published between Jan 2000–Jul 2019 (Figure 1). We assessed available evidence for 2- and 1-dose UMV programs with inactivated HAV vaccine in children worldwide, in terms of impact on HepA incidence, disease severity and mortality, vaccine efficacy, vaccine effectiveness and antibody persistence.Figure 1. PRISMA flowchart Results3739 articles were screened and 34 studies were included in our analysis (Figure 1). 18 real-world studies in 9 countries showed that HepA incidence declined in all ages following introduction of 2-dose and 1-dose UMV programs and persisted for at least 14 years (2-dose) and at least 6 years (1-dose) (Figure 2). Evidence for 1-dose schedule was limited to only 3 studies. HAV related outcomes (disease severity, mortality) decreased after UMV with either 2-dose or 1-dose schedule. Vaccine effectiveness for the 2-dose schedules was ≥ 95% over 3–5 years. Vaccine efficacy for the 1-dose schedule was > 98% over 0.1–7.5 years. Anti-HAV antibody persistence in vaccinated children was documented up to 15 years with ≥ 90% seropositivity rates for the 2-dose schedule and up to 10 years with ≥ 74.3% seropositivity rates for the 1-dose schedule. Anti-HAV antibody GMC data is presented in Table 1.Figure 2. Impact of vaccination on hepatitis A incidence in countries implementing 2-dose or 1-dose schedules (data from studies presenting ‘all ages’ incidence data) Table 1. Anti-HAV antibody GMCs following vaccination with 2-dose and 1-dose schedules, data from studies included in our reviewConclusionThe implementation of 2- and 1-dose UMV programs against HAV induced decreases in disease incidence and related outcomes. Experience with 2-dose schedule is extensive, with wide geographical use, while evidence beyond 10 years for the 1-dose schedule has not yet been demonstrated. Continued and robust surveillance is needed to monitor the epidemiology, vaccine effectiveness, antibody persistence and protection (particularly in the absence of natural boosting) in order to have a strong, scientifically sound basis for decision makers when concluding on HepA prevention strategies in their countries. Funding: GlaxoSmithKline Biologicals SADisclosures Anar Andani, BSc, GSK group of companies (Employee, Shareholder) Eveline M. Bunge, PhD, GSK group of companies (Research Grant or Support) Fernanda Salgado, MD, MSc, GSK group of companies (Employee) Rosa C. van Hoorn, MSc, GSK group of companies (Research Grant or Support) Bernard Hoet, MD, FFPM, GSK group of companies (Shareholder)

The impact of the changing pneumococcal national immunisation program among older Australians

Australia has a universal infant pneumococcal conjugate vaccination program and until recently a universal pneumococcal polysaccharide vaccine program for non-Indigenous adults aged ≥65 years and Indigenous adults aged ≥50 years. We documented the impacts of infant and adult vaccination programs on the epidemiology of invasive pneumococcal disease (IPD) in Indigenous and non-Indigenous adults.IPD notifications from the National Notifiable Disease Surveillance System were analysed from 2002 to 2017, grouped by age, vaccine serotype group and Indigenous status. Since the universal funding of infant and elderly pneumococcal vaccination programs in January 2005, total IPD decreased by 19% in non-Indigenous adults aged ≥65 years but doubled in Indigenous adults aged ≥50 years. Vaccine uptake was suboptimal in both groups but lower in Indigenous adults. IPD due to the serotypes contained in the pneumococcal conjugate vaccines (PCV) except for serotype 3 declined markedly over the study period but were replaced by non-PCV serotypes. Serotype 3 is currently the most common in older adults. In the populations eligible for the adult 23-valent pneumococcal polysaccharide vaccine (23vPPV) program, IPD rates due to its exclusive serotypes increased to a lower extent than non-vaccine types. In 2017, non-vaccine serotypes accounted for most IPD in the older population eligible for the 23vPPV program, while it's eleven exclusive serotypes accounted for the majority of IPD in younger adults.Infant and adult pneumococcal vaccination programs in Australia have shaped the serotype-specific epidemiology of IPD in older adults. IPD remains a significant health burden for the Indigenous population. Herd immunity impact is clear for PCV serotypes excluding serotype 3 and serotype replacement is evident for non-PCV serotypes. The adult 23vPPV immunisation program appears to have partially curbed replacement with IPD due to its eleven exclusive serotypes, highlighting a potential benefit of increasing adult 23vPPV coverage in Australia.

Modeling the epidemiological impact and cost-effectiveness of a combined schoolgirl HPV vaccination and cervical cancer screening program among Chinese women

ABSTRACT Human papillomavirus (HPV) infection is common in women and also the main cause of cervical cancer. Based on a dynamic compartmental model, we aimed to evaluate the population impact and cost-effectiveness of strategies that combined cervical cancer screening and HPV schoolgirl vaccination for Chinese women. The effectiveness of interventions was assessed by comparing modeled scenarios to the status quo, where a 3-y cervical cancer screening program remained at a 20% coverage and without a universal HPV vaccination program. Our study demonstrated that increasing screening coverage from 20% to 50% would reduce the high-risk HPV (HR-HPV) prevalence to 5.4%, whereas a universal schoolgirl vaccination program using the quadrivalent vaccine (qHPV) with a coverage of 50% would reduce the prevalence to 2.9% by 2069. Scaling-up the cervical screening coverage to 50% will prevent 16,012 (95% CI: 8,791 to 25,913) Disability-Adjusted Life-Years (DALYs) per year, with an incremental cost-effectiveness ratio (ICER) of US$ 10,958 (95% CI: $169 to $26,973)/DALY prevented. At the current qHPV price, vaccinating 50% of school girls will prevent 13,854 (95% CI: 8,355 to 20,776) DALYs/year, but the corresponding incremental cost-effectiveness ratio (ICER, US$ 83,043, 95% CI: $52,234 to $138,025) exceeds cost-effectiveness threshold (i.e., 3 times GDP per-capita of China: $30,792). The qHPV vaccine requires at least a 50% price reduction to be cost-effective. Vaccinating schoolgirls will result in a large population health benefit in the long term, but such a universal HPV vaccination program can only be cost-effective with a substantial price reduction.

Effects of Maternal Education on Early Nonmonetary Investments in Child Development

This paper investigates the effects of education on the early investments of mothers in their young children exploiting a compulsory schooling reform in Turkey. I adopt a regression discontinuity design and document that education significantly improves mothers’ prenatal health investments and some postnatal health behavior. However, there is no evidence on the effects of maternal education on breastfeeding duration or compliance with the universal vaccination program. I then show that education leads mothers to spend time with their children at home and outside. These findings suggest that increases in maternal education in a developing country have the potential to reduce inequalities at birth.

PIN13 Cost Minimization and Budget Impact Analysis of Pneumococcal Conjugated Vaccines in 3 Latin American Countries (2020-2024)

Countries in Latin America (LAC) introduced infant Pneumococcal Conjugated Vaccine (PCVs) immunization in their National Immunization Programs (NIPs) following the recommendation of the World Health Organization (WHO). Based on systematic literature reviews and expert opinions, WHO stated there is no evidence of a difference in the net impact of PCVs on overall disease burden, leaving concerns regarding the PCV choice. Therefore, we conducted a budget impact (BI) analysis of the use of PCV10 and PCV13 in Paraguay, Peru and Colombia to address the question of affordability. An excel-based cost calculator was used to estimate the BI of PCVs use in these countries between 2020 and 2024. We compared direct medical cost of the base case scenario (no-vaccine) with the post-vaccine introduction scenario to calculate the BI from the perspective of health care system. In addition, the BI comparing the use of PCV13 and PCV10 was also included. Vaccine prices and vaccine effects were obtained from published data of international organizations. The 5-years BI for PCV10 in Paraguay, Peru and Colombia was -33.3, 83.8 and 100.1 million of United States dollars (USD), respectively, and an incremental BI for PCV13 of 4.9, 14.8 and 21.4 million USD, respectively when compared with PCV10. The use of PCV10 in the NIP of Paraguay, Peru and Colombia will save 70.3, 31.8 and 46.1 million USD respectively in direct medical costs. The analysis found significant differences in the 5-years BI between PCV10 and PCV13, with more than 9 million USD incremental savings on treatments costs and 31.8 million USD incremental savings in vaccine costs for PCV10, in the analyzed countries. These findings can be used in budget planning and to maximize NIP budget. However, to sustain universal mass vaccination programs, policymakers should carefully consider the broader interaction among vaccines and socio-economic development.

Epidemiological Impact and Cost-Effectiveness of Varicella Vaccination Strategies in the United Kingdom.

BackgroundDespite the burden of varicella, there is no universal varicella vaccination (UVV) program in the United Kingdom (UK) due to concerns that it could increase herpes zoster (HZ) incidence. We assessed the cost-utility of a first-dose monovalent (varicella [V]) or quadrivalent (measles-mumps-rubella-varicella [MMRV]) followed by a second-dose MMRV UVV program. GSK and MSD varicella-containing vaccines (VCVs) were considered.MethodsDynamic transmission and cost-effectiveness models were adapted to the UK. Outcomes measured included varicella and HZ incidences and the incremental cost-utility ratio (ICURs) over a lifetime horizon. Payer and societal perspectives were evaluated.ResultsThe impact of V-MMRV and MMRV-MMRV UVV programs on varicella incidence was comparable between both VCVs at equilibrium. HZ incidence increased by 1.6%–1.7% over 7 years after UVV start, regardless of the strategies, then decreased by >95% at equilibrium. ICURs ranged from £5665 (100 years) to £18 513 (20 years) per quality-adjusted life-year (QALY) gained with V-MMRV and from £9220 to £27 101 per QALY gained with MMRV-MMRV (payer perspective). MMRV-MMRV was cost-effective in the medium- and long-terms with GSK VCV and only cost-effective in the long term with MSD VCV at a £20 000 per QALY gained threshold. Without the exogenous boosting hypothesis, HZ incidence decreased through UVV implementation. ICURs were most sensitive to discount rates and MMRV price.ConclusionsA 2-dose UVV was demonstrated to be a cost-effective alternative to no vaccination. With comparable effectiveness as MSD VCV at lower costs, GSK VCV may offer higher value for the money.

Cost-utility analysis of newborn hepatitis B immunization in Beijing

ABSTRACT Objectives To evaluate cost-utility of universal Hepatitis B vaccination program in the Beijing city (Beijing). Methods A decision-Markov model was constructed to determine the cost-utility of the universal immunization program for infants (universal vaccination program) by comparing with a hypothetic nonvaccination strategy in Beijing. Parameters in models were extracted from Beijing Center for Disease Control and Prevention (CDC) annual work report, Beijing health statistical yearbook, National Health Survey report, Beijing 1% population sample survey report, Beijing Health and Medical Price Monitoring Data Platform, and public literatures. The incremental cost‑utility ratio (ICUR) was used to compare alternative scenarios. One-way sensitivity analysis and probabilistic sensitivity analysis were used to assess parameter uncertainties. Results The universal vaccination program had increased the utility and reduced cost among infants born in 2016 in Beijing. The ICUR was CNY −24,576.61 (US$ −3779.16) per QALY for universal vaccination program comparing with non-vaccination scenario from healthcare perspective. It was estimated that the universal vaccination would save direct medical treatment cost of CNY 2,262,869,173.50 (US$ 347,962,414.43) and prevent loss of 18322.25 QALYs within lifetime of target cohort. Discount rate accounted for the most remarkable influence on ICUR in one-way sensitivity analysis. The result of probabilistic sensitivity analysis illustrated that all of the ICURs were located in the fourth quadrant of the cost-utility incremental plot undergone 5000 times of Monte Carlo simulation. Conclusions Current universal hepatitis B vaccination program in Beijing was highly cost utility. The investment was reasonable for current universal vaccination program in Beijing.

The impact of a universal HPV vaccination program on lower genital tract dysplasia and genital warts

Objective: The aim of this study was to assess the impact of Ontario’s school-based human papillomavirus (HPV) vaccination program targeting grade 8 girls on reducing rates of pre-invasive cervical dysplasia, utilization of colposcopy services and treatment rates for genital warts, cervical conization, cryotherapy and laser vaporization of lower-genital-tract pre-invasive dysplasia.

Covid 19 Morbidity and Case Fatality Rate: An Analysis of Possible Confounding Factors

Introduction: When the first report appeared of a protective effect of universal BCG vaccination on COVID- 19 morbidity and case fatality rates, as well as referring to previous papers on the nonspecific protective effects of BCG, our interest was raised, because Mozambique was in an unusual position in relation to BCG vaccination. Based on our knowledge of the history of global public health, we constructed a table with the number of cases of COVID-19 per 100,000 inhabitants and the case fatality rate of the countries that had carried out universal BCG vaccination for a long period (India, Japan and the ex-USSR countries), compared to countries without a universal BCG vaccination programme. We found that countries that had carried out universal BCG vaccination for a long period had much lower case/population ratios and case fatality rates than those without a universal BCG vaccination programme. This exercise was repeated three times, during the month of April, with consistent results. These results made us take the decision to undertake a study of possible confounding factors Mozambique became independent in June 1975, and immediately after carried out a mass vaccination campaign with the six antigens of the recently created EPI. Smallpox vaccine was added, in order to consolidate smallpox eradication. WHO, at that time, was against vaccination campaigns, but an exceptional agreement was obtained. The campaign took place from the north to the south of the country, from February 1976 to January 1978. Every province started a routine EPI programme as soon as the campaign finished. In the campaign, all children 15 years old or younger received BCG vaccine. The coverage rate in the campaign was 97%, with 99% in the capital city of Maputo. Subsequently, the coverage rate of BCG vaccination at birth in the EPI has been always remarkably high in urban areas. In rural areas, coverage has been irregular, but has been at least 80% in the past 25 years. Therefore, most of the urban population aged 58 or less has received BCG, and so has an important part of the rural population. Such a high coverage of BCG is exceedingly rare in the world.

Beyond clinical trials: Evolutionary and epidemiological considerations for development of a universal influenza vaccine.

The prospect of universal influenza vaccines is generating much interest and research at the intersection of immunology, epidemiology, and viral evolution. While the current focus is on developing a vaccine that elicits a broadly cross-reactive immune response in clinical trials, there are important downstream questions about global deployment of a universal influenza vaccine that should be explored to minimize unintended consequences and maximize benefits. Here, we review and synthesize the questions most relevant to predicting the population benefits of universal influenza vaccines and discuss how existing information could be mined to begin to address these questions. We review three research topics where computational modeling could bring valuable evidence: immune imprinting, viral evolution, and transmission. We address the positive and negative consequences of imprinting, in which early childhood exposure to influenza shapes and limits immune responses to future infections via memory of conserved influenza antigens. However, the mechanisms at play, their effectiveness, breadth of protection, and the ability to “reprogram” already imprinted individuals, remains heavily debated. We describe instances of rapid influenza evolution that illustrate the plasticity of the influenza virus in the face of drug pressure and discuss how novel vaccines could introduce new selective pressures on the evolution of the virus. We examine the possible unintended consequences of broadly protective (but infection-permissive) vaccines on the dynamics of epidemic and pandemic influenza, compared to conventional vaccines that have been shown to provide herd immunity benefits. In conclusion, computational modeling offers a valuable tool to anticipate the benefits of ambitious universal influenza vaccine programs, while balancing the risks from endemic influenza strains and unpredictable pandemic viruses. Moving forward, it will be important to mine the vast amount of data generated in clinical studies of universal influenza vaccines to ensure that the benefits and consequences of these vaccine programs have been carefully modeled and explored.

Trends in all-cause pneumonia and otitis media in children aged

ABSTRACT In Colombia, pneumococcal conjugate vaccines (PCVs) were implemented into the infant universal mass vaccination program in a stepwise manner; PCV-7 between 2009 and 2011 in different geographic regions/cities, with nationwide introduction of a 10-valent vaccine (PHiD-CV) in 2012. We aimed to describe trends in all-cause pneumonia mortality and overall mortality, and in the incidence of all-cause pneumonia and otitis media (OM) in Colombian children <2 y (y = years) of age, before and after PCV introduction. We obtained mortality and incidence data, nationally and for five major cities (Bogota, Medellin, Barranquilla, Cali and Cartagena) from 2005–2016 and 2008–2016, respectively, comparing mortality and incidence proportions in the post-PCV introduction period with those in the pre-PCV period. Overall mean reductions in all-cause pneumonia mortality was observed in the post-PCV period nationally (48.8%; 95%CI: 45.5–51.8%) and in four cities including Bogota (77.1%; 71.1–81.8%) and Medellin (56.4%; 44.1–65.9%); no substantial reduction was observed in Cartagena. Similar findings were observed for overall mortality. Reductions in all-cause pneumonia incidence were observed in Bogota (66.0%; 65.5–66.6%), Medellin (40.6%; 39.3–41.9%) and Cartagena (15.0%; 11.2–18.6%), while incidence increased in Barranquilla (78.5%; 68.4–89.2%) and Cali (125.5%; 119.2–132.0%). All-cause OM incidence fell in Medellin and Bogota (42.1–51.1%) but increased (95.8%) in Barranquilla. In conclusion, overall reductions in disease outcomes were observed following PCV introduction in most cities and nationwide. Decreasing trends in outcomes were observed prior to PCV introduction, and limited data points and data reporting issues may have influenced our results. (ClinicalTrials.gov: NCT02567747)