Cost of Illness Analysis of Invasive Meningococcal Disease Caused by Neisseria Meningitidis Serogroup B in the Netherlands-a Holistic Approach.

INTRODUCTION: Invasive meningococcal disease (IMD) caused by Neisseria meningitidis is a rapidly progressing, rare disease that often presents as meningitis or sepsis. It mostly affects infants and adolescents, with high fatality rates or long-term sequelae. In the Netherlands, serogroup B (MenB) is most prevalent. We aimed to estimate the economic burden of MenB-related IMD between 2015 and 2019, including direct and indirect medical costs from short- and long-term sequelae, from a societal perspective. METHODS: IMD incidence was based on laboratory-based case numbers from the Netherlands Reference Laboratory for Bacterial Meningitis (Amsterdam UMC, Amsterdam, the Netherlands); there were 74 MenB cases on average per year in the study period 2015-2019. Case-fatality rate (3.8%) and percentage of patients discharged with sequelae (46%) were derived from literature. Direct costs included treatment costs of the acute phase, long-term sequelae, and public health response. Indirect costs were calculated using the human capital (HCA) and friction costs (FCA) approaches, in which productivity losses were estimated for patients and parents during the acute and sequelae phases. Costs were discounted by 4% yearly. RESULTS: Estimated costs due to MenB IMD in an annual cohort were €3,094,199 with FCA and €9,480,764 with HCA. Direct costs amounted to €2,974,996, of which 75.2% were related to sequelae. Indirect costs related to sequelae were €52,532 with FCA and €5,220,398 with HCA. CONCLUSION: Our analysis reflects the high economic burden of MenB-related IMD in the Netherlands. Sequelae costs represent a high proportion of the total costs. Societal costs were dependent on the applied approach (FCA or HCA).

Reducing Hospital Capacity Needs for Seasonal Respiratory Infections: The Case of Switching to High-Dose Influenza Vaccine for Dutch Older Adults.

OBJECTIVES: Influenza is responsible for considerable health and economic burden every year. Especially older adults are vulnerable for influenza infection and its complications due to immunosenescence and often-underlying medical conditions. Recently, the innovative quadrivalent high-dose influenza vaccine (QIV-HD) has become available in Europe. Through its enhanced immunogenicity, QIV-HD offers improved protection for older adults against respiratory as well as cardiovascular complications. We estimated the potential impact-specifically in terms of hospital admissions and related costs-of a hypothetical past switch from QIV-Standard dose (SD) to QIV-HD in The Netherlands. METHODS: Estimates of hospitalizations for the older adults vaccinated with QIV-SD were derived from the seasons 2010/2011-2017/2018. Subsequently, the number of respiratory infections and cardiovascular complications of influenza were estimated for the year 2019/2020 for both QIV-SD and QIV-HD. To calculate the overall corresponding savings, costs for hospital complications, derived from literature, were used. RESULTS: When QIV-HD would have been used instead of QIV-SD during the season 2019/2020, an additional 220 hospitalizations would have been averted among older adults of 60 years and older in the Netherlands. This corresponds to savings of €1 219 779 (uncertainty interval: 1 089 813-1 348 549), of which 69% is attributable to cardiovascular-related hospitalizations. CONCLUSIONS: We demonstrate that a relevant improvement in influenza vaccination among older adults in The Netherlands can be achieved by switching from the current QIV-SD to QIV-HD. Not only comes a switch from QIV-SD to QIV-HD with a significant reduction in pressure on hospital capacity but also with notable cost savings.

[Rotavirus vaccination for all Dutch infants]. / Rotavirusvaccinatie voor alle jonge kinderen.

Recently, the Netherlands Health Council (HC) issued an updated advice on rotavirus vaccination. Rotavirus gastro-enteritis primarily affects young children, of whom, in the Netherlands, annually ~2700 end up in the hospital and 5-7 die. In 2017, the HC judged positively on rotavirus vaccination of young children, but also concluded that the cost-effectiveness of general vaccination was unfavorable. Yet, the HC recommended to at least vaccinate vulnerable children in specific risk-groups. Because of the corona crisis, this, however, has not materialized. Meanwhile, the Dutch Risk-group Infant Vaccination Against Rotavirus study has demonstrated that rotavirus vaccination of children in risk-groups is less effective than previously thought. Therefore, the HC now recommends rotavirus vaccination of all children. General vaccination within the Dutch NIP is expected to result in herd-immunity, such that all children, including those in risk-groups, are protected. Nonetheless, the Dutch Ministry of Health has decided to postpone implementation of rotavirus vaccination.

[Influenza vaccination: the Netherlands Health Council missed opportunities]. / De griepprik.

Older adults may suffer from severe sequelae of influenza, including not only respiratory but also cardiovascular complications. Innovative influenza vaccines, such as a high-dose vaccine, offer improved protection for the elderly population. Evidence for the enhanced effectiveness and potential cost savings of these vaccines stems from clinical trials and large observational studies, and several countries already recommend their use. Nonetheless, the Netherlands Health Council, in its recent recommendation, judges that the scientific evidence for added value of these improved vaccines is insufficient. Following the recommendation of the WHO of 2012, the council now does include pregnant women in the target groups for influenza vaccination, primarily to improve indirect protection of newborn children. However, judging that the burden of influenza disease among children is relatively modest, the council does not recommend to include healthy children, despite available evidence for favourable effectiveness and cost-effectiveness of paediatric flu vaccination with a live-attenuated vaccine.

Requirement of respiratory support in acute bronchiolitis in infants is linked to endothelial and neutrophil activation.

BACKGROUND: Evidence shows that activation of pulmonary vascular endothelium and neutrophils are involved in the pathophysiology of acute bronchiolitis. We hypothesized that levels of markers of endothelial activation and leukocyte counts are associated with requirement and duration of respiratory support. METHODS: Thirty-four infants with bronchiolitis and eight controls were included. Nasopharyngeal swabs and blood samples were taken at admission. Serum levels of Angiopoietin (Ang)-1, Ang-2, sP-selectin, sE-selectin, vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1), and leukocyte counts were measured. For univariate analysis, bronchiolitis cases were grouped into two groups, namely those not requiring and those requiring any form of respiratory support. To control for known risk factors for poor outcome (i.e., age, prematurity, and congenital heart disease), and for days post symptom onset, linear regression analysis was performed with duration of any type of respiratory support in days. RESULTS: Ang-2 levels, Ang-2/Ang-1 ratios, sE-selectin levels, immature neutrophil count, and neutrophil/lymphocyte ratio (NLR) were higher in acute bronchiolitis versus controls. Ang-2, and NLR levels were significantly higher, and lymphocyte counts significantly lower, in infants that required respiratory support versus those that did not. Ang-2 levels (ß: .32, 95% confidence interval [CI]: 0.19-1.19) and NLR (ß: .68, 95% CI: 0.17-1.19) were positive predictors for the duration of respiratory support. CONCLUSIONS: Markers of endothelial and neutrophil activation are associated with respiratory support for acute bronchiolitis. Admission Ang-2 levels and NLR may be promising markers to determine requirement of respiratory support and deserve further study.

Viral causes of severe acute respiratory infection in hospitalized children and association with outcomes: A two-year prospective surveillance study in Suriname.

BACKGROUND: Viruses are the most frequent cause of severe acute respiratory infection (SARI) in children. It is currently unknown whether presence of a virus, the number of viruses, or type of virus, are associated with clinical outcomes of pediatric SARI in developing countries. METHODS: Between 2012 and 2014 nasopharyngeal swabs and demographic and clinical variables were prospectively collected for surveillance of viral causes of SARI in Surinamese children within 48 hours after hospitalization. These swabs were tested for 18 respiratory viruses using a multiplex polymerase chain reaction (PCR) panel to identify the specific viral causes of SARI, unknown to the treating physicians. In post hoc analyses we evaluated if the PCR results, and demographic and clinical characteristics, were associated with course of disease, duration of respiratory support, and length of stay (LOS). RESULTS: Of a total of 316 analyzed children, 290 (92%) had one or more viruses. Rhinovirus/enterovirus (43%) and respiratory syncytial virus (34%) were most prevalent. Course of disease was mild in 234 (74%), moderate in 68 (22%), and severe in 14 (4%) children. Neither presence of a single virus, multiple viruses, or the type of virus, were different between groups. Prematurity and lower weight-for-age-z-score were independent predictors of a severe course of disease, longer duration of respiratory support, and longer LOS. CONCLUSIONS: Viruses are common causes of pediatric SARI in Suriname, yet not necessarily associated with clinical outcomes. In developing countries, demographic and clinical variables can help to identify children at-risk for worse outcome, while PCR testing may be reserved to identify specific viruses, such as influenza, in specific patient groups or during outbreaks.

Rotavirus Vaccination of Infants Delayed and Limited within the National Immunization Programme in the Netherlands: An Opportunity Lost.

In this study, we estimated the benefits of rotavirus vaccination for infants had the rotavirus vaccine been introduced in the Netherlands as of its market authorization in 2006. An age-structured, deterministic cohort model was developed to simulate different birth cohorts over a period of 15 years from 2006 until 2021, comparing both universal and targeted high-risk group vaccination to no vaccination. Different scenarios for the duration of protection (5 or 7 years) and herd immunity (only for universal vaccination) were analyzed. All birth cohorts together included 2.6 million infants, of which 7.9% were high-risk individuals, and an additional 13.2 million children between 1-15 years born prior to the first cohort in 2006. The costs and health outcomes associated with rotavirus vaccination were calculated per model scenario and discounted at 4% and 1.5%, respectively. Our analysis reveals that, had rotavirus vaccination been implemented in 2006, it would have prevented 356,800 (51% decrease) and 32,200 (5% decrease) cases of rotavirus gastroenteritis after universal and targeted vaccination, respectively. Over the last 15 years, this would have led to significant avoided costs and quality-adjusted life year losses for either vaccination strategy with the most favorable outcomes for universal vaccination. Clearly, an opportunity has been lost.

Cost-Effectiveness of Pediatric Influenza Vaccination in The Netherlands.

OBJECTIVE: This study evaluates the cost-effectiveness of extending the Dutch influenza vaccination program for elderly and medical high-risk groups to include pediatric influenza vaccination, taking indirect protection into account. METHODS: An age-structured dynamic transmission model was used that was calibrated to influenza-associated GP visits over 4 seasons (2010-2011 to 2013-2014). The clinical and economic impact of different pediatric vaccination strategies were compared over 20 years, varying the targeted age range, the vaccine type for children or elderly and high-risk groups. Outcome measures include averted symptomatic infections and deaths, societal costs and quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. Costs and QALYs were discounted at 4% and 1.5% annually. RESULTS: At an assumed coverage of 50%, adding pediatric vaccination for 2- to 17-year-olds with quadrivalent live-attenuated vaccine to the current vaccination program for elderly and medical high-groups with quadrivalent inactivated vaccine was estimated to avert, on average, 401 820 symptomatic cases and 72 deaths per year. Approximately half of averted symptomatic cases and 99% of averted deaths were prevented in other age groups than 2- to 17-year-olds due to herd immunity. The cumulative discounted 20-year economic impact was 35 068 QALYs gained and €1687 million saved, that is, the intervention was cost-saving. This vaccination strategy had the highest probability of being the most cost-effective strategy considered, dominating pediatric strategies targeting 2- to 6-year-olds or 2- to 12-year-olds or strategies with trivalent inactivated vaccine. CONCLUSION: Modeling indicates that introducing pediatric influenza vaccination in The Netherlands is cost-saving, reducing the influenza-related disease burden substantially.

Cost-effectiveness of hepatitis C virus screening, and subsequent monitoring or treatment among pregnant women in the Netherlands.

BACKGROUND: The prevalence of diagnosed chronic hepatitis C virus (HCV) infection among pregnant women in the Netherlands is 0.26%, yet many cases remain undiagnosed. HCV screening and treatment of pregnant HCV carriers could reduce the burden of disease and limit vertical transmission from mother to child. We assessed the impact of HCV screening and subsequent treatment with new direct-acting antivirals (DAAs) among pregnant women in the Netherlands. METHODS: An HCV natural history Markov transition state model was developed, to evaluate the public-health and economic impact of HCV screening and treatment. Besides all 179,000 pregnant women in the Netherlands (cohort 1), we modelled 3 further cohorts: all 79,000 first-time pregnant women (cohort 2), 33,000 pregnant migrant women (cohort 3) and 16,000 first-time pregnant migrant women (cohort 4). Each cohort was analyzed in various scenarios: i no intervention, i.e., the current practice, ii screen-and-treat, i.e., the most extensive approach involving treatment of all individuals found HCV-positive, and iii screen-and-treat/monitor, i.e., a strategy involving treatment of symptomatic (F1-F4) patients and follow-up of asymptomatic (F0) HCV carriers with subsequent treatment only at progression. RESULTS: For all cohorts, comparison between scenarios (ii) and (i) resulted in ICERs between €9,306 and €10,173 per QALY gained and 5 year budget impacts varying between €6,283,830 and €19,220,405. For all cohorts, comparison between scenarios (iii) and (i) resulted in ICERs between €1,739 and €2,749 per QALY gained and budget impacts varying between €1,468,670 and €5,607,556. For all cohorts, the ICERs (scenario iii versus ii) involved in delayed treatment of asymptomatic (F0) HCV carriers varied between €56,607 and €56,892, well above the willingness-to-pay (WTP) threshold of €20,000 per QALY gained and even above a threshold of €50,000 per QALY gained. CONCLUSION: Universal screening for HCV among all pregnant women in the Netherlands is cost-effective. However, it would be reasonable to consider smaller risk groups in view of the budget impact of the intervention.

First-in-Human Phase I Clinical Trial of an SFV-Based RNA Replicon Cancer Vaccine against HPV-Induced Cancers.

A first-in-human phase I trial of Vvax001, an alphavirus-based therapeutic cancer vaccine against human papillomavirus (HPV)-induced cancers was performed assessing immunological activity, safety, and tolerability. Vvax001 consists of replication-incompetent Semliki Forest virus replicon particles encoding HPV16-derived antigens E6 and E7. Twelve participants with a history of cervical intraepithelial neoplasia were included. Four cohorts of three participants were treated per dose level, ranging from 5 × 105 to 2.5 × 108 infectious particles per immunization. The participants received three immunizations with a 3-week interval. For immune monitoring, blood was drawn before immunization and 1 week after the second and third immunization. Immunization with Vvax001 was safe and well tolerated, with only mild injection site reactions, and resulted in both CD4+ and CD8+ T cell responses against E6 and E7 antigens. Even the lowest dose of 5 × 105 infectious particles elicited E6/E7-specific interferon (IFN)-γ responses in all three participants in this cohort. Overall, immunization resulted in positive vaccine-induced immune responses in 12 of 12 participants in one or more assays performed. In conclusion, Vvax001 was safe and induced immune responses in all participants. These data strongly support further clinical evaluation of Vvax001 as a therapeutic vaccine in patients with HPV-related malignancies.

The Cost-Effectiveness of Hepatitis C Virus Screening Strategies among Recently Arrived Migrants in the Netherlands.

OBJECTIVE: We aimed to assess the cost-effectiveness of hepatitis C virus (HCV) screening strategies among recently arrived migrants in the Netherlands. METHODS: A Markov model was used to estimate the health effects and costs of HCV screening from the healthcare perspective. A cohort of 50,000 recently arrived migrants was used. In this cohort, three HCV screening strategies were evaluated: (i) no screening, (ii) screening of migrants from HCV-endemic countries and (iii) screening of all migrants. RESULTS: Strategy (ii) screening of migrants from HCV-endemic countries compared to strategy (i) no screening, yielded an incremental cost-effectiveness ratio (ICER) of €971 per quality-adjusted life-years (QALYs) gained. Strategy (iii) screening of all migrants compared with strategy (ii) screening of migrants from HCV-endemic countries yielded an ICER of €1005 per QALY gained. The budget impact of strategy (ii) screening of migrants from HCV-endemic countries and strategy (iii) screening of all migrants was €13,752,039 and €20,786,683, respectively. CONCLUSION: HCV screening is cost-effective. However, the budget impact may have a strong influence on decision making.

[Continue to use the bivalent HPV vaccine; bivalent vaccine more effective than expected]. / Blijf het bivalente HPV-vaccin gebruiken.

It is becoming clear that there are significant differences between the two principal human papillomavirus (HPV) vaccines, namely the bivalent vaccine and the quadrivalent vaccine. Both vaccines contain HPV16 and HPV18, together responsible for approximately 73% of cases of cervical cancer. The quadrivalent vaccine also contains HPV6 and HPV11, thus protecting against genital warts. Real-world data show 89% efficacy for the bivalent vaccine against cervical intraepithelial neoplasia stage 3, irrespective of the HPV type involved, versus 64% for the quadrivalent vaccine. This suggests superior cross-reactivity of the bivalent vaccine against oncogenic HPV types not contained in the vaccine, presumably thanks to the MPLA adjuvant in the vaccine. In the Netherlands, the cross-reactivity of the bivalent vaccine may ultimately lead to a significant additional reduction of cervical cancer deaths per year. Since protection against genital warts should not be pursued at the expense of protection against cervical cancer, we recommend that the Netherlands continue to use the bivalent vaccine in its national immunisation programme.

Factors associated with the uptake of newly introduced childhood vaccinations in Ethiopia: the cases of rotavirus and pneumococcal conjugate vaccines.

BACKGROUND: Childhood immunization programmes have made substantial contributions to lowering the burden of disease among children in developing countries, however a large proportion of children still remain unimmunized. This study aimed to explore the determinants of rotavirus vaccine (RVV) and pneumococcal conjugate vaccine (PCV) uptake in Ethiopia. METHODS: The 2016 Ethiopian demographic and health survey dataset was used in this analysis. A total of 2004 children aged 12-23 months were included in the analysis. A multivariable logistic regression model was employed to identify the determinants of uptake of the complete schedules of RVV (two doses) and PCV (three doses). Crude and adjusted odds ratios with 95% confidence intervals (CIs) were calculated. RESULTS: The uptakes of the complete schedules of RVV and PCV among children aged 12-23 months were 56 and 49.1%, respectively. The likelihood of immunization with the complete schedule of RVV was significantly lower among children from the relatively poor Afar region in Ethiopia (AOR 0.16; 95%-CI 0.04-0.61). Similarly, children living in not only the Afar region (AOR 0.10; 95%-CI 0.03-0.38), but also the Gambela region (AOR 0.25; 95%-CI 0.08-0.83), were less likely to be vaccinated with PCV. On the other hand, children from more wealthy households had higher odds of vaccination with RVV (AOR 1.69; 95%-CI 1.04-2.75). Also attending antenatal care (ANC) was found to be significantly associated with uptake of the complete schedule of RVV and PCV. CONCLUSIONS: The uptake of RVV and PCV is suboptimal in Ethiopia. The uptake of the vaccines were found to be associated with region, ANC use and wealth status.

Respiratory syncytial virus subunit vaccines based on the viral envelope glycoproteins intended for pregnant women and the elderly.

Introduction: Respiratory syncytial virus (RSV) causes high morbidity and mortality rates among infants, young children, and the elderly worldwide. Unfortunately, a safe and effective vaccine is still unavailable. In 1966, a formalin-inactivated RSV vaccine failed and resulted in the death of two young children. This failure shifted research toward the development of subunit-based vaccines for pregnant women (to passively vaccinate infants) and the elderly. Among these subunit-based vaccines, the viral envelope glycoproteins show great potential as antigens. Areas covered: In this review, progress in the development of safe and effective subunit RSV vaccines based on the viral envelope glycoproteins and intended for pregnant women and the elderly, are reviewed and discussed. Studies published in the period 2012-2018 were included. Expert opinion: Researchers are close to bringing safe and effective subunit-based RSV vaccines to the market using the viral envelope glycoproteins as antigens. However, it remains a major challenge to elicit protective immunity, with a formulation that has sufficient (storage) stability. These issues may be overcome by using the RSV fusion protein in its pre-fusion conformation, and by formulating this protein as a dry powder. It may further be convenient to administer this powder via the pulmonary route.

Cost-effectiveness of vaccination of immunocompetent older adults against herpes zoster in the Netherlands: a comparison between the adjuvanted subunit and live-attenuated vaccines.

BACKGROUND: The newly registered adjuvanted herpes zoster subunit vaccine (HZ/su) has a higher efficacy than the available live-attenuated vaccine (ZVL). National decision-makers soon need to decide whether to introduce HZ/su or to prefer HZ/su above ZVL. METHODS: Using a Markov model with a decision tree, we conducted a cost-effectiveness analysis of vaccination with HZ/su (two doses within 2 months) or zoster vaccine live (ZVL) (single dose, or single dose with a booster after 10 years) for cohorts of 50-, 60-, 70- or 80-year-olds in the Netherlands. The model was parameterized using vaccine efficacy data from randomized clinical trials and up-to-date incidence, costs and health-related quality of life data from national datasets. We used a time horizon of 15 years, and the analysis was conducted from the societal perspective. RESULTS: At a coverage of 50%, vaccination with two doses of HZ/su was estimated to prevent 4335 to 10,896 HZ cases, depending on the cohort age. In comparison, this reduction was estimated at 400-4877 for ZVL and 427-6466 for ZVL with a booster. The maximum vaccine cost per series of HZ/su to remain cost-effective to a willingness-to-pay threshold of €20,000 per quality-adjusted life year (QALY) gained ranged from €109.09 for 70-year-olds to €63.68 for 50-year-olds. The cost-effectiveness of ZVL changed considerably by age, with corresponding maximum vaccine cost per dose ranging from €51.37 for 60-year-olds to €0.73 for 80-year-olds. Adding a ZVL booster after 10 years would require a substantial reduction of the maximum cost per dose to remain cost-effective as compared to ZVL single dose. Sensitivity analyses on the vaccine cost demonstrated that there were scenarios in which vaccination with either HZ/su (two doses), ZVL single dose or ZVL + booster could be the most cost-effective strategy. CONCLUSIONS: A strategy with two doses of HZ/su was superior in reducing the burden of HZ as compared to a single dose or single dose + booster of ZVL. Both vaccines could potentially be cost-effective to a conventional Dutch willingness-to-pay threshold for preventive interventions. However, whether HZ/su or ZVL would be the most cost-effective alternative depends largely on the vaccine cost.

A systematic review of the health economic consequences of quadrivalent influenza vaccination.

BACKGROUND: Quadrivalent influenza vaccines (QIVs) contain antigens derived from an additional influenza type B virus as compared with currently used trivalent influenza vaccines (TIVs). This should overcome a potential reduced vaccine protection due to mismatches between TIV and circulating B viruses. In this study, we systematically reviewed the available literature on health economic evaluations of switching from TIV to QIV. Areas covered: The databases of Medline and Embase were searched systematically to identify health economic evaluations of QIV versus TIV published before September 2016.A total of sixteen studies were included, thirteen cost-effectiveness analyses and three cost-comparisons. Expert commentary: Published evidence on the cost-effectiveness of QIV suggests that switching from TIV to QIV would be a valuable intervention from both the public health and economic viewpoint. However, more research seems mandatory. Our main recommendations for future research include: 1) more extensive use of dynamic models in order to estimate the full impact of QIV on influenza transmission including indirect effects, 2) improved availability of data on disease outcomes and costs related to influenza type B viruses, and 3) more research on immunogenicity of natural influenza infection and vaccination, with emphasis on cross-reactivity between different influenza B viruses and duration of protection.

Immunogenicity and safety of human papillomavirus (HPV) vaccination in Asian populations from six countries: a meta-analysis.

Cervical cancer is a serious public-health problem in Asian countries. Since human papillomavirus (HPV) infection is the main risk factor for cervical cancer, HPV vaccination is considered a promising strategy to prevent cervical cancer. However, comprehensive immunogenicity and safety information for Asian populations is lacking. We searched four electronic databases including PubMed, EMBASE, Cochrane Library, and clinicaltrials.gov. We reviewed selected manuscripts and extracted the pooled relative risk (RR) from immunogenicity and safety information on HPV vaccination among women in Asian countries. We identified two quadrivalent-vaccine studies and eight bivalent-vaccine studies conducted in Asian countries. Analysis across these studies suggested that the HPV vaccines significantly enhanced HPV16- and HPV18-specific antibody among both uninfected (RR 85.69; 95% confidence interval (CI) 31.51-233.04 and 62.77; 95% CI 37.4-105.51) and infected individuals (RR 8.60; 95% CI 6.95-10.64 and RR 8.13; 95% CI 5.96-11.11). Furthermore, HPV vaccination among Asian populations has a favorable safety profile, with only slightly higher risks of local (RR: 1.89; 95% CI 1.65-2.17) and systemic (RR: 1.33; 95% CI 1.18-1.50) adverse events in vaccinated individuals compared with controls. For Asian populations, HPV vaccines enhance the level of HPV16- and HPV18-specific antibodies for both uninfected and infected individuals. Also, the risk of adverse events related to vaccination are acceptable. More data are needed to establish vaccine efficacy with regard to prevention of HPV infection and further outcomes including cervical intraepithelial neoplasia (CIN) and cervical cancer.

Cost-Utility Analysis of Human Papillomavirus Vaccination and Cervical Screening on Cervical Cancer Patient in Indonesia.

BACKGROUND: Although cervical cancer is a preventable disease, the clinical and economic burdens of cervical cancer are still substantial issues in Indonesia. OBJECTIVES: The main purpose of this study was to model the costs, clinical benefits, and cost-utility of both visual inspection with acetic acid (VIA) screening alone and human papillomavirus (HPV) vaccination in addition to VIA screening in Indonesia. METHODS: We developed a population-based Markov model, consisting of three health states (susceptible, cervical cancer, and death), to assess future costs, health effects, and the cost-utility of cervical cancer prevention strategies in Indonesia. We followed a cohort of 100,000 females 12 to 100 years old and compared VIA screening alone with the addition of HPV vaccination on top of the screening to "no intervention." RESULTS: The implementation of VIA screening alone and in combination with HPV vaccination would reduce the cervical cancer incidence by 7.9% and 58.5%, corresponding to 25 and 98 deaths avoided within the cohort of 100,000, respectively. We also estimated that HPV vaccination combined with VIA screening apparently yielded a lower incremental cost-effectiveness ratio at international dollar 1863/quality-adjusted life-year (QALY), compared with VIA screening alone (I$3126/QALY). Both strategies could however be definitely labeled as very cost-effective interventions, based on a threshold suggested by the World Health Organization. The incremental cost-effectiveness ratio was sensitive to the discount rate, cervical cancer treatment costs, and quality of life as part of the QALY. CONCLUSIONS: The addition of HPV vaccination on top of VIA screening could be a cost-effective strategy in Indonesia even if relatively conservative assumptions are applied. This population-based model can be considered as an essential tool to inform decision makers on designing optimal strategies for cervical cancer prevention in Indonesia.

Three atypical lethal cases associated with acute Zika virus infection in Suriname.

Acute Zika virus infection usually presents with a self-limiting triad of fever, rash and arthritis. There is limited information on severe or lethal cases. We report three cases of lethal acute Zika infection, confirmed with polymerase chain reaction, in adult patients with some co-morbidities. The patients showed rapid clinical deterioration with hemorrhagic and septic shock, and exaggerated acute and innate inflammatory responses with pronounced coagulopathy, and died soon after admission to the hospital. It remains unclear whether the fatal outcomes were due to acute Zika virus infection alone or to the combination with exacerbated underlying prior disease or co-infection. Nonetheless, the severity of these cases implies that increased awareness for atypical presentations of Zika virus infection, and careful clinical assessment of patients with symptoms of Zika, is warranted during current and future outbreaks.

Assessment of the Broader Economic Consequences of HPV Prevention from a Government-Perspective: A Fiscal Analytic Approach.

BACKGROUND: Cervical cancer poses a substantial burden in terms of morbidity, mortality, and economic losses, especially in low/middle-income countries. HPV vaccination and/or cervical cancer screening among females may reduce the burden of HPV-related diseases, including cervical cancer. However, limited funds may impede the implementation of population-based programmes. Governmental investments in the prevention of infectious disease may have broader economic and fiscal benefits, which are not accounted in conventional economic analyses. This study estimates the broader economic and fiscal impacts of implementing HPV vaccination and/or cervical cancer screening in Indonesia from the perspective of the government. METHODS: A government-perspective quantitative analytic framework was applied to assess the Net Present Value (NPV) of investment on cervical cancer prevention strategies including HPV vaccination, cervical screening and its combination in Indonesia. All monetary values were presented in International Dollars (I$). RESULTS: Based on a cohort of 10,000,000 Indonesian 12-year-old females, it was estimated that HPV vaccination and/or cervical cancer screening result in a positive NPV for the Indonesian government. The combination of cervical screening and HPV vaccination generated a substantial reduction of cervical cancer incidence and HPV-related mortality of 87,862 and 19,359, respectively. It was estimated that HPV vaccination in combination with cervical screening is the most favorable option for cervical cancer prevention (NPV I$2.031.786.000), followed by HPV vaccination alone (NPV I$1.860.783.000) and cervical screening alone (NPV I$375.244.000). CONCLUSION: In addition to clinical benefits, investing in HPV vaccination and cervical screening may yield considerable fiscal benefits for the Indonesian governments due to lifelong benefits resulting from reduction of cervical cancer-related morbidity and mortality.