The association between influenza vaccination uptake and influenza and pneumonia-associated deaths in the United States.

BACKGROUND: The influenza mortality burden has remained substantial in the United States (US) despite relatively high levels of influenza vaccine uptake. This has led to questions regarding the effectiveness of the program against this outcome, particularly in the elderly. The aim of this evaluation was to develop and explore a new approach to estimating the population-level effect of influenza vaccination uptake on pneumonia and influenza (P&I) associated deaths. METHODS: Using publicly available data we examined the association between state-level influenza vaccination and all-age P&I associated deaths in the US from the 2013-2014 influenza season to the 2018-2019 season. In the main model, we evaluated influenza vaccine uptake in all those age 6 months and older. We used a mixed-effects regression analysis with generalised least squares estimation to account for within state correlation in P&I mortality. RESULTS: From 2013-2014 through 2018-2019, the total number of all-age P&I related deaths during the influenza seasons was 480,111. The mean overall cumulative influenza vaccine uptake (age 6 months and older) across the states and years considered was 46.7%, with higher uptake (64.8%) observed in those aged ≥ 65 years. We found that overall influenza vaccine uptake (6 months and older) had a statistically significant protective association with the P&I death rate. This translated to a 0.33 (95% CI: 0.20, 0.47) per 100,000 population reduction in P&I deaths in the influenza season per 1% increase in overall influenza vaccine uptake. DISCUSSION: These results using a population-level statistical approach provide additional support for the overall effectiveness of the US influenza vaccination program. This reassurance is critical given the importance of ensuring confidence in this life saving program. Future research is needed to expand on our approach using more refined data.

Incremental effectiveness of 23-valent pneumococcal polysaccharide vaccine against pneumonia hospitalisation among Australian Indigenous children: A record linkage study.

BACKGROUND: The impact of pneumococcal conjugate vaccines (PCVs) on pneumonia in children is well-documented but data on 23-valent pneumococcal polysaccharide vaccine (PPV23) are lacking. Between 2001 and 2011, Indigenous children in Western Australia (WA) were recommended to receive PPV23 at 18-24 months of age following 3 doses of 7-valent PCV. We evaluated the incremental effectiveness of PPV23 against pneumonia hospitalisation. METHODS: Indigenous children born in WA between 2001 and 2012 who received PCV dose 3 by 12 months of age were followed from 18 to 60 months of age for the first episode of pneumonia hospitalisation (all-cause and 3 subgroups: presumptive pneumococcal, other specified causes, and unspecified). We used Cox regression modelling to estimate hazard ratios (HRs) for pneumonia hospitalisation among children who had, versus had not, received PPV23 between 18 and 30 months of age after adjustment for confounders. RESULTS: 11,120 children had 327 first episodes of all-cause pneumonia hospitalisation, with 15 (4.6%) coded as presumptive pneumococcal, 46 (14.1%) as other specified causes and 266 (81.3%) unspecified. No statistically significant reduction in all-cause pneumonia was seen with PPV23 (HR 1.11; 95% CI: 0.87-1.43), but the direction of the association differed for presumptive pneumococcal (HR 0.47; 95% CI: 0.16-1.35) and specified (HR 0.89; 95% CI: 0.49-1.62) from unspecified causes (HR 1.13; 95% CI: 0.86-1.49). During the baseline period before PPV23 vaccination (12-18 months), all-cause pneumonia risk was higher among PPV23-vaccinated than unvaccinated children (RR: 1.73; 95% CI: 1.30-2.28). CONCLUSION: In this high-risk population, no statistically significant incremental effect of a PPV23 booster at 18-30 months was observed against hospitalised all-cause pneumonia or the more specific outcome of presumptive pneumococcal pneumonia. Confounding by indication may explain the slight trend towards an increased risk against all-cause pneumonia. Larger studies with better control of confounding are needed to further inform PPV23 vaccination.

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).

Modelled estimates of hospitalisations attributable to respiratory syncytial virus and influenza in Australia, 2009-2017.

BACKGROUND: Respiratory syncytial virus (RSV) and influenza are important causes of disease in children and adults. In Australia, information on the burden of RSV in adults is particularly limited. METHODS: We used time series analysis to estimate respiratory, acute respiratory infection, pneumonia and influenza, and bronchiolitis hospitalisations attributable to RSV and influenza in Australia during 2009 through 2017. RSV and influenza-coded hospitalisations in <5-year-olds were used as proxies for relative weekly viral activity. RESULTS: From 2009 to 2017, the estimated all-age average annual rates of respiratory hospitalisations attributable to RSV and seasonal influenza (excluding 2009) were 54.8 (95% confidence interval [CI]: 20.1, 88.8) and 87.8 (95% CI: 74.5, 97.7) per 100,000, respectively. The highest estimated average annual RSV-attributable respiratory hospitalisation rate per 100,000 was 464.2 (95% CI: 285.9, 641.2) in <5-year-olds. For seasonal influenza, it was 521.6 (95% CI: 420.9, 600.0) in persons aged ≥75 years. In ≥75-year-olds, modelled estimates were approximately eight and two times the coded estimates for RSV and seasonal influenza, respectively. CONCLUSIONS: RSV and influenza are major causes of hospitalisation in young children and older adults in Australia, with morbidity underestimated by hospital diagnosis codes.

Effectiveness of 7-Valent Pneumococcal Conjugate Vaccine Against Invasive Pneumococcal Disease in Medically At-Risk Children in Australia: A Record Linkage Study.

BACKGROUND: Children with chronic medical conditions are at higher risk of invasive pneumococcal disease (IPD), but little is known about the effectiveness of the primary course of pneumococcal conjugate vaccine (PCV) in these children. METHODS: A cohort born in 2001-2004 from two Australian states and identified as medically at-risk (MAR) of IPD either using ICD-coded hospitalizations (with conditions of interest identified by 6 months of age) or linked perinatal data (for prematurity) were followed to age 5 years for notified IPD by serotype. We categorized fully vaccinated children as either receiving PCV dose 3 by <12 months of age or ≥1 PCV dose at ≥12 months of age. Cox proportional hazard modeling was used to estimate hazard ratios (HRs), adjusted for confounders, and vaccine effectiveness (VE) was estimated as (1-HR) × 100. RESULTS: A total of 9220 children with MAR conditions had 53 episodes of IPD (43 vaccine-type); 4457 (48.3%) were unvaccinated and 4246 (46.1%) were fully vaccinated, with 1371 (32.3%) receiving dose 3 by 12 months and 2875 (67.7%) having ≥1 dose at ≥12 months. Estimated VE in fully vaccinated children was 85.9% (95% CI: 33.9-97.0) against vaccine-type IPD and 71.5% (95% CI: 26.6-88.9) against all-cause IPD. CONCLUSION: This is the first population-based study evaluating the effectiveness of PCV in children with MAR conditions using record linkage. Our study provides evidence that the VE for vaccine-type and all-cause IPD in MAR children in Australia is high and not statistically different from previously reported estimates for the general population. This method can be replicated in other countries to evaluate VE in MAR children.

Influenza-associated mortality in Australia, 2010 through 2019: High modelled estimates in 2017.

INTRODUCTION: In Australia, the 2017 and 2019 influenza seasons were severe. High-dose or adjuvanted vaccines were introduced for ≥65 year-olds in 2018. AIM: To compare influenza-associated mortality in 2017 and 2019 with the average for 2010-2019. METHODS: We used time series modelling to obtain estimates of influenza-associated death rates for influenza A(H1N1)pdm09, A(H3N2) and B in Australia, in persons of all ages and <65, 65-74 and ≥75 years. Estimates were made for pneumonia and influenza (P&I, 2010-2018), respiratory (2010-2018), and all-cause outcomes (2010-2019). RESULTS: During 2010 through 2018 (and 2019 for all-cause), influenza was estimated to be associated with an annual average of 2.1 (95% confidence interval (CI) 1.9, 2.4), 4.0 (95% CI 3.4, 4.6), and 11.6 (95% CI 8.4, 15.0) P&I, respiratory and all-cause deaths per 100,000 population, respectively. Influenza A(H1N1)pdm09 was estimated to be associated with less than one quarter of influenza-associated P&I and respiratory deaths, while A(H3N2) and B were each estimated to contribute approximately equally to the remaining influenza-associated deaths. In 2017, the respective rates were 7.8 (95% CI 7.1, 8.4), 12.3 (95% CI 10.9, 13.6) and 26.0 (95% CI 20.8, 32.0) per 100,000. In 2019, the all-cause estimate was 20.8 (95% CI 14.9, 26.7) per 100,000. CONCLUSIONS: Seasonal influenza continues to be associated with substantial mortality in Australia, with at least double the average occurring in 2017. Age-specific monitoring of vaccine effectiveness is needed in Australia to understand higher mortality seasons.

Estimating pertussis incidence in general practice using a large Australian primary care database.

BACKGROUND: While pertussis is notifiable in most countries, notifications typically underestimate the true pertussis burden. We explored the incidence of pertussis in general practice in Australia. METHODS: Using MedicineInsight, a large longitudinal electronic medical record database of general practice (primary care) encounters which includes >1.5 million patients, we first defined a cohort of active patients and then used free-text search algorithms to identify patients with pertussis-related encounters. We defined and identified pertussis-related encounters in four patient categories: pertussis-associated (category 1), potential pertussis (category 2), epidemiologically-linked pertussis (category 3), and symptoms consistent with pertussis (category 4). Incident pertussis-related encounter rates per 100,000 active patients were calculated from Jan 2008 to Aug 2015. RESULTS: Estimated mean annual pertussis incidence increased as definitions were expanded, from 94.3 (category 1 patients only) to 148.8 (categories 1+2+3 patients combined) per 100,000 active patients per year. Monthly time-series corresponding to the first three categories were highly correlated (Pearson's r > 90% for each pair), but each was poorly correlated with category 4. For categories 1+2+3, the highest incidence was among 0-4 and 5-9 year olds. Incidence was 30% higher in females than males (i.e. 184.5 vs 139.8 per 100,00 active patients for categories 1-3 patients combined). Pertussis-associated incidence (category 1) was similar to national pertussis notification rates. Categories 2 and 3 added 25% and 33%, respectively, on average relative to category 1 incidence. The estimated incidence from categories 1+2+3 together were on average 64% higher than national pertussis notification rates. CONCLUSION: We provide comprehensive estimates of pertussis-related incidence in general practice (primary care), well in excess of notified pertussis incidence in Australia. This highlights the utility of MedicineInsight data in providing a greater understanding of the burden of medically-attended pertussis infections.

Rotavirus Vaccination Likely to Be Cost Saving to Society in the United States.

BACKGROUND: Following the introduction of rotavirus immunization in 2006 in the United States, there were substantial declines in the domestic rotavirus disease burden. In this study, we assess the value for money achieved by the program in the decade following vaccine introduction. METHODS: We applied an age-specific, static, multicohort compartmental model to examine the impact and cost-effectiveness of the US rotavirus immunization program in children <5 years of age using healthcare utilization data from 2001 to 2015 inclusive. We calculated the incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) gained from both a healthcare system and societal perspective. RESULTS: Declines in healthcare use associated with the rotavirus and acute gastroenteritis occurred from 2006 and continued to grow before stabilizing from 2010 through 2011. From 2011 to 2015, an estimated annual average of approximately 118 000 hospitalizations, 86 000 emergency department presentations, and 460 000 outpatient and physician office visits were prevented. From a societal perspective during this same period, the program was estimated to be cost saving in the base case model and in >90% of probabilistic sensitivity analysis simulations and from a healthcare system perspective >98% of simulations found an ICER below $100 000 per QALY gained. CONCLUSIONS: After the program stabilized, we found the rotavirus immunization in the United States was likely to have been cost saving to society. The greater than expected healthcare and productivity savings reflect the success of the rotavirus immunization program in the United States.

Cost-effectiveness of statins for primary prevention of atherosclerotic cardiovascular disease among people living with HIV in the United States.

BACKGROUND: Expanding statin use may help to alleviate the excess burden of atherosclerotic cardiovascular disease in people living with HIV (PLHIV). Pravastatin and pitavastatin are preferred agents due to their lack of substantial interaction with antiretroviral therapy. We aimed to evaluate the cost-effectiveness of pravastatin and pitavastatin for the primary prevention of atherosclerotic cardiovascular disease among PLHIV in the United States. METHODS: We developed a microsimulation model that randomly selected (with replacement) individuals from the Data-collection on Adverse Effects of Anti-HIV Drugs study with follow-up between 2013 and 2016. Our study population was PLHIV aged 40 to 75 years, stable on antiretroviral therapy, and not currently using lipid-lowering therapy. Direct medical costs and quality-adjusted life-years (QALYs) were assigned in annual cycles and discounted at 3% per year. We assumed a willingness-to-pay threshold of $100,000/QALY gained. The interventions assessed were as follows: (1) treating no one with statins; (2) treating everyone with generic pravastatin 40 mg/day (drug cost $236/year) and (3) treating everyone with branded pitavastatin 4 mg/day (drug cost $2,828/year). The model simulated each individual's probability of experiencing atherosclerotic cardiovascular disease over 20 years. RESULTS: Persons receiving pravastatin accrued 0.024 additional QALYs compared with those not receiving a statin, at an incremental cost of $1338, giving an incremental cost-effectiveness ratio of $56,000/QALY gained. Individuals receiving pitavastatin accumulated 0.013 additional QALYs compared with those using pravastatin, at an additional cost of $18,251, giving an incremental cost-effectiveness ratio of $1,444,000/QALY gained. These findings were most sensitive to the pill burden associated with daily statin administration, statin costs, statin efficacy and baseline atherosclerotic cardiovascular disease risk. In probabilistic sensitivity analysis, no statin was optimal in 5.2% of simulations, pravastatin was optimal in 94.8% of simulations and pitavastatin was never optimal. CONCLUSIONS: Pravastatin was projected to be cost-effective compared with no statin. With substantial price reduction, pitavastatin may be cost-effective compared with pravastatin. These findings bode well for the expanded use of statins among PLHIV in the United States. To gain greater confidence in our conclusions it is important to generate strong, HIV-specific estimates on the efficacy of statins and the quality-of-life burden associated with taking an additional daily pill.

Estimating pneumococcal vaccine coverage among Australian Indigenous children and children with medically at-risk conditions using record linkage.

BACKGROUND: Risk-based recommendations are common for pneumococcal vaccines but little is known about their uptake. In Australia, pneumococcal conjugate vaccine (PCV) was funded only for Aboriginal or Torres Strait Islander (Indigenous) children and those with underlying medical conditions in 2001, and then there were different booster dose recommendations depending on risk after the introduction of universal PCV vaccination in 2005. METHODS: We measured coverage of PCV dose 3 and additional PCV and 23-valent pneumococcal polysaccharide vaccine (PPV23) doses by risk group among children born in July 2001-December 2012 in two Australian states using linked immunisation and hospitalisation data (available until December 2013). We ascertained medical risk conditions using hospitalisation diagnosis codes and Indigenous status using an established algorithm, comparing coverage for children born pre (2001-2004) and post (2005-2012) universal PCV funding. RESULTS: Among 1.3 million children, 63,897 (4.9%) were Indigenous and 32,934 (2.5%) had at least one medically at-risk condition identified by age 6 months. For births in 2001-2004, coverage for PCV dose 3 by 1 year of age was 37% for Indigenous, 15% for medically at-risk and 11% in other children, increasing to 83%, 91% and 92%, respectively for births in 2005-2012. In children with medically at-risk conditions, PCV dose 4 coverage by 2 years was 1% for 2001-2004 births, increasing to 9% for 2005-2012 births, with PPV23 coverage by 6 years 3% in both cohorts. Among eligible Indigenous children, PPV23 coverage by 3 years was 45% for 2001-2004 births and 51% for 2005-2012 births. CONCLUSIONS: Coverage with additional recommended booster doses was very low among children with medical conditions, and only modest among Indigenous children. If additional PCV doses are recommended for some risk groups, especially in the context of routine schedules with reduced doses (e.g. 2 + 1 and 1 + 1), measures to improve implementation will be required.

Global production capacity of seasonal and pandemic influenza vaccines in 2019.

Vaccines will be an important element in mitigating the impact of an influenza pandemic. While research towards developing universal influenza vaccines is ongoing, the current strategy for vaccine supply in a pandemic relies on seasonal influenza vaccine production to be switched over to pandemic vaccines. Understanding how much vaccine could be produced, in which regions of the world and in what timeframe is critical to informing influenza pandemic preparedness. Through the Global Action Plan for Influenza Vaccines, 2006-2016, WHO promoted an increase in vaccine production capacity and monitors the landscape through periodically surveying influenza vaccine manufacturers. This study compares global capacity for production of influenza vaccines in 2019 with estimates from previous surveys; provides an overview of countries with established production facilities; presents vaccine production by type and manufacturing process; and discusses limitations to these estimates. Results of the current survey show that estimated annual seasonal influenza vaccine production capacity changed little since 2015 increasing from 1.47 billion to 1.48 billion doses with potential maximum annual influenza pandemic vaccine production capacity increasing from 6.37 billion to 8.31 billion doses. However, this figure should be interpreted with caution as it presents a best-case scenario with several assumptions which may impact supply. Further, pandemic vaccines would not be immediately available and could take four to six months for first supplies with several more months needed to reach maximum capacity. A moderate-case scenario is also presented of 4.15 billion doses of pandemic vaccine in 12 months. It is important to note that two doses of pandemic vaccine are likely to be required to elicit an adequate immune response. Continued efforts are needed to ensure the sustainability of this production and to conduct research for vaccines that are faster to produce and more broadly protective taking into account lessons learned from COVID-19 vaccine development.

Statins for atherosclerotic cardiovascular disease prevention in people living with HIV in Thailand: a cost-effectiveness analysis.

INTRODUCTION: People living with HIV (PLHIV) have an elevated risk of atherosclerotic cardiovascular disease (CVD) compared to their HIV-negative peers. Expanding statin use may help alleviate this burden. However, the choice of statin in the context of antiretroviral therapy is challenging. Pravastatin and pitavastatin improve cholesterol levels in PLHIV without interacting substantially with antiretroviral therapy. They are also more expensive than most statins. We evaluated the cost-effectiveness of pravastatin and pitavastatin for the primary prevention of CVD among PLHIV in Thailand who are not currently using lipid-lowering therapy. METHODS: We developed a discrete-state microsimulation model that randomly selected (with replacement) individuals from the TREAT Asia HIV Observational Database cohort who were aged 40 to 75 years, receiving antiretroviral therapy in Thailand, and not using lipid-lowering therapy. The model simulated each individual's probability of experiencing CVD. We evaluated: (1) treating no one with statins; (2) treating everyone with pravastatin 20mg/day (drug cost 7568 Thai Baht ($US243)/year) and (3) treating everyone with pitavastatin 2 mg/day (drug cost 8182 Baht ($US263)/year). Direct medical costs and quality-adjusted life-years (QALYs) were assigned in annual cycles over a 20-year time horizon and discounted at 3% per year. We assumed the Thai healthcare sector perspective. RESULTS: Pravastatin was estimated to be less effective and less cost-effective than pitavastatin and was therefore dominated (extended) by pitavastatin. Patients receiving pitavastatin accumulated 0.042 additional QALYs compared with those not using a statin, at an extra cost of 96,442 Baht ($US3095), giving an incremental cost-effectiveness ratio of 2,300,000 Baht ($US73,812)/QALY gained. These findings were sensitive to statin costs and statin efficacy, pill burden, and targeting of PLHIV based on CVD risk. At a willingness-to-pay threshold of 160,000 Baht ($US5135)/QALY gained, we estimated that pravastatin would become cost-effective at an annual cost of 415 Baht ($US13.30)/year and pitavastatin would become cost-effective at an annual cost of 600 Baht ($US19.30)/year. CONCLUSIONS: Neither pravastatin nor pitavastatin were projected to be cost-effective for the primary prevention of CVD among PLHIV in Thailand who are not currently using lipid-lowering therapy. We do not recommend expanding current use of these drugs among PLHIV in Thailand without substantial price reduction.

High healthcare resource utilisation due to pertussis in Australian adults aged 65 years and over.

BACKGROUND: In the context of co-morbid illness and increasing age, data on excess morbidity from pertussis in older adults is crucial for immunisation policy but has been largely limited to case-series. METHODS: We designed a matched case-control study nested within a population-based cohort of 267,153 adults aged ≥45 years in New South Wales, Australia (The 45 and Up Study cohort). Excess hospital bed days, emergency department (ED) admissions, general practitioner (GP) visits, and prescriptions were estimated using negative binomial regression models. An additional self-controlled analysis was also conducted to validate the main models, and to evaluate results for those with either asthma or a body mass index (BMI)≥30 compared to those without these risk factors. RESULTS: Based on 524 pairs of PCR-confirmed pertussis cases and matched controls, we estimated an excess healthcare utilisation per case of 2.5 prescriptions (95% CI: 0.2-4.7), of which 1.1 (95% CI: 0.5-2.2) were antibiotics, 2.3 GP visits (95% CI: 2.0-2.6), and 0.1 ED admissions (95% CI: 0.1-0.2). Compared to those 45-64 years, cases ≥65 years had a significantly greater excess for all prescriptions (1.1 vs 4.7/case), antibiotic prescriptions (0.1 vs 2.2/case), and ED admissions (0.1 vs 0.2/case), but no significant excess of respiratory-related hospital bed days. An additional self-controlled analysis confirmed that cases with either asthma or BMI≥30 had higher overall healthcare utilisation but this was not associated with pertussis infection. CONCLUSION: We found a substantial excess outpatient healthcare burden among adults aged 65 years and over with PCR-confirmed pertussis, supporting further evaluation of preventive measures.

Effectiveness of Acellular Pertussis Vaccine in Older Adults: Nested Matched Case-control Study.

BACKGROUND: Despite recommendations that older adults receive acellular pertussis vaccines, data on direct effectiveness in adults aged over 50 years are sparse. METHODS: A case-control study nested within an adult cohort. Cases were identified from linked pertussis notifications and each matched to 3 controls on age, sex, and cohort recruitment date. Cases and controls were invited to complete a questionnaire, with verification of vaccination status by their primary care provider. Vaccine effectiveness (VE) was estimated by conditional logistic regression, with adjustment for reported contact with children and area of residence. RESULTS: Of 1112 notified cases in the cohort, we had complete data for 333 cases and 506 controls. Among 172 PCR-diagnosed cases (mean age, 61 years), 11.2% versus 19.5% of controls had provider-verified pertussis vaccination, on average, 3.2 years earlier. Adjusted VE against PCR-diagnosed pertussis was 52% (95% CI, 15-73%), nonsignificantly higher if vaccinated within 2 years (63%; -5-87%). Adjusted VE was similar in adults born before 1950, presumed primed by natural infection (51%; -8-77%) versus those born 1950 or later who may have received whole-cell pertussis vaccine (53%; -11-80%) (P-heterogeneity = 0.9). Among 156 cases identified by single-point serology, adjusted VE was -55% (-177-13%). CONCLUSIONS: We found modest protection against PCR-confirmed pertussis among older adults (mean age, 61 years; range, 46-81 years) within 5 years after acellular vaccine. The most likely explanation for the markedly divergent VE estimate from cases identified by single-titer serology is misclassification arising from limited diagnostic specificity in our setting.

Financial cost analysis of a strategy to improve the quality of administrative vaccination data in Uganda.

BACKGROUND: High-quality vaccination data are critical to planning, implementation and evaluation of immunization programs. However, sub-optimal administrative vaccination data quality in low- and middle-income countries persist for heterogeneous reasons, though most relate to organizational factors and human behavior. The nationwide Data Improvement Team (DIT) strategy in Uganda aimed to strengthen human resource capacity to generate quality administrative vaccination data at the health facility. METHODS: A financial cost analysis of the Uganda DIT strategy (2014-2016) was conducted from the program funder perspective. Activity-based micro-costing from funder financial and program monitoring records was used to estimate total and unit costs by program area (in 2016 US dollars). Hypothetical scenarios were developed to illustrate potential approaches to reducing costs. RESULTS: Over 25 months the DIT strategy was implemented in all 116 operational districts and 3443 (89%) health facilities in Uganda at a total financial cost of US $575 275. Training and deployment of DITs accounted for the highest proportion of expenditure across program areas (69%). Transport, per diems, lodging, and honoraria for DIT members and national supervisors were the main cost drivers of the strategy. Deployment of 557 DIT members cost US $839 per DIT member, US $4 030 per district, and US $136 per health facility. The estimated opportunity cost of government staff time wasn't a major cost driver (2.5%) of total cost. CONCLUSION: The results provide the first estimates of the magnitude and drivers of cost to implement a national workforce capacity building strategy to improve administrative vaccination data quality in a low- or middle-income country. Financial costs are a critical input to combine with future outcome data to describe the cost of strategies relative to performance outcomes. The operational costs of the strategy were modest (0.5-1.6%) relative to the estimated operational costs of Uganda's national immunization program.

Rapid mapping of the spatial and temporal intensity of influenza.

Surveillance of influenza epidemics is a priority for risk assessment and pandemic preparedness, yet representation of their spatiotemporal intensity remains limited. Using the epidemic of influenza type A in 2016 in Australia, we demonstrated a simple but statistically sound adaptive method of mapping epidemic evolution over space and time. Weekly counts of persons with laboratory confirmed influenza type A infections in Australia in 2016 were analysed by official national statistical region. Weekly standardised epidemic intensity was represented by a standard score (z-score) calculated using the standard deviation of below-median counts in the previous 52 weeks. A geographic information system (GIS) was used to present the epidemic progression. There were 79,628 notifications of influenza A infections included. Of these, 79,218 (99.5%) were allocated to a geographical area. The GIS maps indicated areas of elevated epidemic intensity across Australia by week and area that were consistent with the observed start, peak and decline of the epidemic when compared with counts aggregated at the state and territory level. This simple, adaptable approach could improve local level epidemic intelligence in a variety of settings and for other diseases. It may also facilitate increased understanding of geographic epidemic dynamics.

Recent advances in the development of monoclonal antibodies for rabies post exposure prophylaxis: A review of the current status of the clinical development pipeline.

Despite successful control in many parts of the world, rabies virus continues to result in tens of thousands of deaths each year. Death from rabies can be prevented by timely and appropriate post exposure prophylaxis including wound cleaning and administration of vaccine and rabies immunoglobulin. Currently, rabies immunoglobulin is derived from the blood plasma of horses or humans and has several limitations relating to supply, cost and quality. Monoclonal antibodies produced through recombinant DNA technologies could potentially overcome these limitations. The first anti-rabies monoclonal antibody has recently gained regulatory approval in India and there are several other candidates being evaluated in clinical trials. Given the advances in the field, rabies monoclonal antibodies have been recently considered by the World Health Organization's Strategic Advisory Group of Experts on Immunization and included in updated WHO immunization policy recommendations for rabies published in April 2018. This article reviews the current landscape of the clinical trial development of anti-rabies monoclonal antibodies and the historical clinical trial pathways followed for blood-derived rabies immunoglobulin before discussing challenges in the clinical evaluation, regulatory approval, uptake and monitoring of these products.