Economic Evaluation of Human Rotavirus Vaccine in Thailand Abstract Introduction Rotavirus gastroenteritis is the leading cause of severe diarrhoea among young children < 5 years old. Previous cost-effectiveness analyses on rotavirus (RV) vaccination in Thailand have generated conflicting results. The aim of this current study is to evaluate the economic impact of introducing RV vaccination in Thailand, using updated Thai epidemiological and cost data. Methods Both cost-utility analysis (CUA) and budget impact analysis (BIA) of human rotavirus vaccine (HRV) under a universal mass vaccination (UMV) programme were conducted. A published static, deterministic, cross-sectional population model was adapted to assess costs and health outcomes associated with RV vaccination among Thai children < 5 years old during 1 year for CUA and over a 5-year period (2019–2023) for BIA. Data identified through literature review were incorporated into the model after consultation with local experts. Base case CUA was conducted from a societal perspective with quality-adjusted life year (QALY) discounted at 3% annually. Scenario analyses as well as one-way and probabilistic sensitivity analyses were conducted to assess the robustness of the base case CUA results. Costs were updated to 2017. Results At 99% coverage, HRV vaccination would substantially reduce RV-related disease burden. With an incremental cost-effectiveness ratio (ICER) of Thai baht (THB) 49,923/QALY gained, HRV vaccination versus no vaccination was cost-effective when assessed against a local threshold of THB 160,000/QALY gained. Scenario and sensitivity analyses confirmed the cost-effectiveness with all resultant ICERs falling below the willingness-to-pay threshold. HRV use in the UMV programme was estimated to result in a net expenditure of about THB 255–281 million to the Thai government in the 5th year of the programme, depending on vaccine uptake. Conclusion HRV vaccination is estimated to be cost-effective in Thailand. The budget impact following inclusion of HRV into the UMV programme is expected to be partially offset by substantial reductions in RV-related disease costs. Funding GlaxoSmithKline Biologicals SA GSK Study Identifier HO-17-18213

Passive Screening and Diagnosis of Sleeping Sickness with New Tools in Primary Health Services: An Operational Research Abstract Introduction The integration of human African trypanosomiasis (HAT) activities into primary health services is gaining importance as a result of the decreasing incidence of HAT and the ongoing developments of new screening and diagnostic tools. In the Democratic Republic of Congo, this integration process faces multiple challenges. We initiated an operational research project to document drivers and bottlenecks of the process. Methods Three health districts piloted the integration of HAT screening and diagnosis into primary health services. We analysed the outcome indicators of this intervention and conducted in-depth interviews with health care providers, seropositives, community health workers and HD management team members. Our thematic interview guide focused on factors facilitating and impeding the integration of HAT screening. Results The study showed a HAT-RDT-positive rate of 2.2% in Yasa Bonga, 2.9% in Kongolo and 3% in Bibanga, while the proportion of reported seropositives that received confirmatory examinations was 76%, 45.6% and 68%, respectively. Qualitative analyses indicated that some seropositives were unable to access the confirmation facility. The main reasons that were given included distance, RDT rupture, lack of basic screening equipment and financial barriers (additional hospital fees not included in free treatment course), fear of lumbar puncture and the perception of HAT as a disease of supernatural origin. Conclusion Passive screening using HAT RDTs in primary health services inevitably has some limitations. However, regarding the epidemiological context and some obstacles to integrated implementation, this cannot on its own be a relevant alternative to the elimination of HAT by 2020. Funding We acknowledge the agency that provided financial support for this study, the Belgian Development Cooperation. The funder had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. Philippe Mulenga received financial support thanks to a doctoral grant from the Belgian Development Cooperation under the FA4 agreement. Funding for the study and Rapid Service Fees was provided by the Epidemiology and Tropical Diseases Unit of the Institute of Tropical Medicine, Antwerp.

Clinical Features of Bloodstream Infections Associated with Peripheral Versus Central Venous Catheters Abstract Introduction This study aimed to compare the clinical characteristics and prognoses of central venous catheter-associated bloodstream infections (CVC-BSIs) with peripheral venous catheter-associated BSIs (PVC-BSIs). Methods This retrospective observational study was conducted between April 2011 and March 2013 at a teaching hospital in Tokyo, Japan. Adult patients who developed CVC-BSIs and PVC-BSIs more than 2 days after admission were included. Patients with both CVC-BSIs and PVC-BSIs were excluded. Clinical characteristics of patients with CVC-BSIs and PVC-BSIs were obtained from medical records, and 30-day all-cause mortality was measured as the clinical outcome. Results We enrolled 124 PVC-BSI cases and 110 CVC-BSI cases. Median age, age-adjusted Charlson score, Sequential Organ Failure Assessment score, sex, and ward type at BSI onset did not differ significantly between the two groups. The median duration of catheter indwelling was significantly shorter in the PVC-BSI group than in the CVC-BSI group. Staphylococcus aureus and Gram-negative bacilli infections were more frequent and coagulase-negative staphylococci (CNS) and Candida spp. infections were less frequent in the PVC-BSI group than in the CVC-BSI group. The prevalence of oxacillin resistance among causative S. aureus and CNS, 30-day all-cause mortality, and appropriateness of empirical and definitive antimicrobial therapies did not differ significantly between the two groups. Conclusion The pathogen species distribution varies between PVC-BSIs and CVC-BSIs. However, all-cause mortality does not differ between the two groups. PVCs are not safer than CVCs with respect to BSIs; therefore, it is necessary to use similar precautions relevant to CVC use in order to avoid unnecessary use of PVCs.

Risk Factors Associated with Linkage to Care among Suburban Hepatitis C-Positive Baby Boomers and Injection Drug Users Abstract Introduction Suffolk County, located in Eastern Long Island, has been an epicenter for the opioid epidemic in New York State, yet no studies have examined hepatitis C virus (HCV) prevalence in this population. Additionally, few studies have assessed barriers for linkage to care (LTC) to HCV treatment in people who inject drugs (PWID), a high-risk HCV cohort. We aimed to determine prevalence of HCV infection in a suburban medical center and to assess risk factors associated with LTC in HCV-positive baby boomers and young PWID. Methods A retrospective chart review was carried out on adult patients with ICD-9/10 diagnostic codes for HCV from January 2016 to December 2018 at Stony Brook Medicine. Data collected included sociodemographics, RNA serostatus, LTC, health insurance, employment, past medical or psychiatric history, and substance or injection drug use. Results Overall, 27,049 individuals were screened for HCV and 1017 were HCV seropositive (3.8%), 437 (42.9%) were HCV RNA-positive and 153 (40.6%) achieved LTC. In multivariate analysis, living with cirrhosis was associated with a positive LTC. Medicaid or Medicare insurance was associated with a negative LTC. Intravenous drug users were more likely to be young and have concomitant polysubstance use and psychiatric disease. A bimodal distribution of HCV-positives is present in our population. Conclusion Those with liver cirrhosis are more likely to achieve LTC, as are those with private insurance. Public health efforts to promote awareness of HCV and to facilitate access to treatment among PWID are needed.

Evaluation of Plazomicin, Tigecycline, and Meropenem Pharmacodynamic Exposure against Carbapenem-Resistant Enterobacteriaceae in Patients with Bloodstream Infection or Hospital-Acquired/Ventilator-Associated Pneumonia from the CARE Study (ACHN-490-007) Abstract Introduction CARE was a Phase 3, randomized study evaluating the efficacy and safety of plazomicin-based combination therapy compared with colistin-based combination therapy for the treatment of patients with bloodstream infections or hospital-acquired/ventilator-associated pneumonia due to carbapenem-resistant Enterobacteriaceae (CRE). Adjunctive therapies included either tigecycline or meropenem. We sought to understand the contribution of tigecycline and meropenem to plazomicin-treated-patient outcomes by determining their observed pharmacodynamic exposures against baseline pathogens. Methods Blood samples collected for plazomicin therapeutic monitoring were assayed for tigecycline and meropenem concentrations. Population pharmacokinetic models were constructed for each antibiotic. Using the individual Bayesian posterior or a covariate-based model, concentration time profiles were simulated to estimate the pharmacodynamic exposures for each patient. Pharmacodynamic thresholds for plazomicin, tigecycline, and meropenem were a total area under the curve to minimum inhibitory concentration ratio (AUC/MIC) ≥ 85, free (f) AUC/MIC ≥ 0.9, and free time above the MIC (fT > MIC) of ≥ 40%, respectively. Results Fifteen plazomicin-treated patients were included (12 received tigecycline, 4 received meropenem, 1 received both). Microbiological response was observed in 13 (86.7%) and clinical efficacy was achieved in 11 (73.3%). Plazomicin achieved its pharmacodynamic target in all 15 patients. Meropenem fT > MIC was 0% in all 4 patients, and tigecycline fAUC/MIC was ≥ 0.9 in 9 (75%) patients. Overall, 6 (40%) of 15 patients had a tigecycline or meropenem exposure below the requisite thresholds. Microbiological response and clinical efficacy were observed in 100% (6/6) and 83.3% (5/6) of patients with low threshold attainment by tigecycline and meropenem dosing regimens, respectively. Conclusions Plazomicin successfully achieved its requisite pharmacodynamic exposure, and these data suggest that optimization of tigecycline and meropenem therapy was not required for the combination to achieve microbiological response and clinical efficacy against serious CRE infections. Trial Registration ClinicalTrials.gov number, NCT01970371. Funding Achaogen, Inc.

Long-Term Serological Response to 13-Valent Pneumococcal Conjugate Vaccine Versus 23-Valent Polysaccharide Vaccine in HIV-Infected Adults Abstract Introduction Long-term comparative immunologic response to 13-valent pneumococcal conjugate vaccine (PCV13) versus 23-valent polysaccharide vaccine (PPV23) among HIV-infected adults has not yet been investigated. Methods In this prospective pilot study, we quantified in HIV-positive adults serotype-specific IgG concentrations of the 12 pneumococcal serotypes shared by both vaccines 5 years after vaccination with two doses of PCV13 8 weeks apart (group 1) or one dose of PPV23 (group 2) and compared them with those assessed prior to vaccination (BL) and after 1 year (T1). Comparison of immunogenicity was based on geometric mean concentration (GMC), proportion of individuals with ≥ twofold increase from BL in specific antibody concentration against ≥ 2 serotypes and percentage of individuals with serotype-specific IgG ≥ 0.35 μg/ml, ≥ 1 μg/ml and ≥ individual serotype-specific correlates of protection. Results We included 91 subjects (median CD4+ 650 cells/µl, > 90% with HIV-RNA < 50 copies/ml); patients in groups 1 (n = 42) and 2 (n = 49) were homogeneous for the main characteristics. GMCs were significantly higher in the PCV13 group than in the PPV23 group for serotype 19F (p = 0.003). Both vaccines revealed higher significant GMCs to most serotypes compared with BL, i.e., eight in group 1 vs. seven in group 2. With respect to T1, GMCs decreased significantly in the PCV13 group for eight vs. ten serotypes in the PPV23 group. More participants in the PCV13 group had ≥ 2 increase from BL in antibody levels to ≥ 2 serotypes compared with the PPV23 group (78.6% vs. 59.2%, p = 0.042). Overall, the percentage of subjects with serotype-specific IgG ≥ 0.35 μg/ml, ≥ 1 μg/ml and ≥ individual serotype-specific correlates of protection was similar between groups. Conclusion In this study with HIV-positive adults with a favorable viro-immunologic profile, both vaccines were shown to achieve a long-term durable serologic response. We found minor differences in immunogenicity between the two vaccines, which favored PCV13 over PPV23 5 years after immunization. Trial Registration ClinicalTrials.gov identifier, NCT02123433.

Epidemiologic Trends, Global Shifts in Meningococcal Vaccination Guidelines, and Data Supporting the Use of MenACWY-TT Vaccine: A Review Abstract Neisseria meningitidis is a major cause of meningitis and septicemia with cases, outbreaks, and epidemics reported globally in industrialized and non-industrialized countries. N. meningitidis is categorized into 12 serogroups; however, only 5 serogroups (A, B, C, W, Y) are responsible for the majority of disease. Invasive meningococcal disease (IMD) occurs unpredictably; protection is therefore best achieved by initiating proactive vaccination strategies. Vaccines are currently available for the five main disease-causing serogroups. With the evolution of meningococcal vaccines and changes in IMD epidemiology, different vaccination strategies have been used. Recently, the rapid clonal expansion of meningococcal serogroup W (MenW) has been associated with a change in the national and regional vaccination recommendations from monovalent meningococcal serogroup C vaccines to meningococcal serogroup A, C, W, Y (MenACWY) vaccines in several countries. This review highlights these and other changes in IMD epidemiology and meningococcal vaccination recommendations, summarizes information available for currently available conjugate MenACWY vaccines, and focuses on clinical study data for the most recently approved MenACWY conjugate vaccine, MenACWY vaccine conjugated to tetanus toxoid (MenACWY-TT). MenACWY-TT studies spanned multiple age groups and generally demonstrated safety and immunogenicity in comparison with other meningococcal vaccines and under concomitant administration of other routine vaccines. Continuous updates to meningococcal vaccine recommendations in response to changing epidemiology, as have been undertaken for MenW, are necessary to ensure optimal population protection. Funding Pfizer, Inc.

Immunogenicity of a Quadrivalent Human Papillomavirus Vaccine When Co-Administered with Tetanus-Reduced Diphtheria-Acellular Pertussis and Quadrivalent Meningococcal Conjugate Vaccines in Healthy Adolescents: Results from a Randomized, Observer-Blind, Controlled Trial Abstract Introduction Vaccines against human papillomavirus (HPV), tetanus, diphtheria, pertussis (Tdap) and Neisseria meningitidis are widely recommended in adolescents. A phase-4 observer-blind study was performed to investigate the impact of concomitant administration of a quadrivalent HPV (HPV4) and Tdap vaccine with a quadrivalent meningococcal CRM197-conjugate vaccine (MenACWY-CRM) in terms of immunogenicity against the different vaccine antigens and overall safety profile. Previous results showed that concomitant administration of the three vaccines did not impact the immunogenicity of Tdap and MenACWY, or safety. This article presents recently released HPV immunogenicity results. Methods Healthy adolescents aged 11–18 years (801) were randomized to receive either HPV4 + Tdap + MenACWY or HPV4 + Tdap + Placebo and two additional doses of HPV4 at 2 and 6 months after the first dose. Antibody responses to HPV types (HPV-6, -11, -16 and -18) were assessed at baseline and at 1 month post-full vaccination. Results Post-third HPV4 dose, non-inferiority of immune responses to HPV4 + Tdap + MenACWY vs. HPV4 + Tdap + Placebo was demonstrated; the lower limits of two-sided 95% CIs of the between-group differences in seroconversion rates were > − 5% (non-inferiority margin) against each HPV type tested. Seroconversion rates ranged between 98.0% (HPV-6) and 99.7% (HPV-11 and HPV-18) in group HPV4 + Tdap + MenACWY and from 99.0% (HPV-11 and HPV-16) to 99.7% (HPV-6 and HPV-18) in group HPV4 + Tdap + Placebo. Conclusion Overall, these data support the concomitant administration of HPV4, Tdap and MenACWY-CRM in adolescents. Funding Novartis Vaccines and Diagnostics Inc., now part of the GSK group of companies. Trial Registration ClinicalTrials.gov identifier, NCT01424644.

The Influence of Patient Experience with Healthcare on the Health-Related Quality of Life of People Living with HIV: An Observational Cross-Sectional Survey Abstract Introduction Patient experience is central to the quality of healthcare delivery, showing positive associations with several outcome measures. The main objectives of this study are to analyze the influence of patient experience on the health-related quality of life in people living with HIV and the role played by treatment complexity and clinical care. Methods We conducted a cross-sectional survey with 467 patients with HIV. We used the Instrument for Evaluation of the Experience of Chronic Patients and the Health-related Quality of Life Questionnaire (EQ-5D-5L). We analyzed a predictive model through the partial least squares (PLS) method. Results The patient self-management scores showed the highest positive relationship with the patient’s health-related quality of life (β = 0.24, β = 0.32, p < 0.0001). Patients’ treatment complexity had a negative influence on health-related quality of life (β = − 0.21, β = − 0.28, p < 0.0001). The complexity of clinical care had negative effects on health-related quality of life, both directly (β = − 0.37, β = − 0.19, p < 0.0001) and through its negative influence on the productive interactions with healthcare professionals (β = − 0.21, p < 0.0001) and patient self-management factors (β = − 0.21, p < 0.0001). The effects of patient experience dimensions on their health-related quality of life were higher in people living with HIV > 50 years old (p < 0.05). Conclusions Patient experience mainly influenced the health-related quality of life of older people living with HIV. The treatment and clinical care complexity played an important role in degrading the patients' experience and their quality of life. More integrated care would benefit the health-related quality of life of people living with HIV. Funding This project was funded by Merck Sharp & Dohme, Spain.

Telavancin in Hospital-Acquired and Ventilator-Associated Pneumonia (HAP/VAP) Caused by Staphylococcus aureus : Post Hoc Analysis of 2 Randomized, Controlled Trials Abstract Introduction The efficacy and safety of telavancin versus vancomycin in microbiologically evaluable patients with hospital-acquired or ventilator-associated pneumonia (HAP/VAP) caused by Staphylococcus aureus with vancomycin minimum inhibitory concentration (MIC) ≥ 1.0 µg/mL was analyzed using data derived from previously reported Assessment of Telavancin for Treatment of Hospital-Acquired Pneumonia (ATTAIN) trials. Methods This post hoc subgroup analysis of two randomized, double-blind, comparator-controlled, parallel-group phase 3 trials conducted at 274 sites in 38 countries included 194 microbiologically evaluable patients with HAP/VAP caused by monomicrobial S. aureuswith vancomycin MIC ≥ 1.0 µg/mL. Patients received intravenous telavancin (10 mg/kg every 24 h) or intravenous vancomycin (1 g every 12 h with site-specific modifications) for 7–21 days. Efficacy was assessed by clinical cure, defined as improvement or non-progression of radiographic findings at end of treatment and resolution of pneumonia signs and symptoms at follow-up/test-of-cure visits, and survival 28 days post-randomization. Safety was assessed from categorical shifts in creatinine clearance during therapy and adverse events (AEs). Results Clinical cure rates were numerically greater following telavancin versus vancomycin treatment overall (85.4% vs. 74.3%; treatment difference [95% confidence interval (CI)], 11.1% [− 0.002%, 22.2%]) and in patients aged ≥ 65 years (81.6% vs. 66.2%; treatment difference [95% CI], 15.5% [− 0.9%, 30.2%]) patients with VAP (92.3% vs. 47.6%; treatment difference [95% CI], 44.7% [18.1%, 64.9%]), and patients with baseline Acute Physiology And Chronic Health Evaluation II score ≥ 20 (71.4% vs. 55.6%; treatment difference [95% CI], 15.9% [− 11.7%, 40.5%]). Renal function declined in 7 (7.9%) patients receiving telavancin and 6 (5.7%) patients receiving vancomycin. Survival proportion was numerically higher (85.2% vs. 80.2%; treatment difference [95% CI], 5.0% [− 5.8%, 15.8%]) and AEs were comparable in patients treated with telavancin versus vancomycin. Conclusion Telavancin is an alternative to vancomycin for HAP/VAP caused by S. aureus with vancomycin MIC ≥ 1 µg/mL. Funding Theravance Biopharma R&D, Inc., South San Francisco, CA, USA.