COVID-19 vaccination in Sindh Province,Pakistan: A modelling study of health impact and cost-effectiveness

BackgroundMultiple Coronavirus Disease 2019 (COVID-19) vaccines appear to be safe and efficacious, but only high-income countries have the resources to procure sufficient vaccine doses for most of their eligible populations. The World Health Organization has published guidelines for vaccine prioritisation, but most vaccine impact projections have focused on high-income countries, and few incorporate economic considerations. To address this evidence gap, we projected the health and economic impact of different vaccination scenarios in Sindh Province, Pakistan (population: 48 million).Methods and findingsWe fitted a compartmental transmission model to COVID-19 cases and deaths in Sindh from 30 April to 15 September 2020. We then projected cases, deaths, and hospitalisation outcomes over 10 years under different vaccine scenarios. Finally, we combined these projections with a detailed economic model to estimate incremental costs (from healthcare and partial societal perspectives), disability-adjusted life years (DALYs), and incremental cost-effectiveness ratio (ICER) for each scenario.We project that 1 year of vaccine distribution, at delivery rates consistent with COVAX projections, using an infection-blocking vaccine at $3/dose with 70% efficacy and 2.5-year duration of protection is likely to avert around 0.9 (95% credible interval (CrI): 0.9, 1.0) million cases, 10.1 (95% CrI: 10.1, 10.3) thousand deaths, and 70.1 (95% CrI: 69.9, 70.6) thousand DALYs, with an ICER of $27.9 per DALY averted from the health system perspective. Under a broad range of alternative scenarios, we find that initially prioritising the older (65+) population generally prevents more deaths. However, unprioritised distribution has almost the same cost-effectiveness when considering all outcomes, and both prioritised and unprioritised programmes can be cost-effective for low per-dose costs. High vaccine prices ($10/dose), however, may not be cost-effective, depending on the specifics of vaccine performance, distribution programme, and future pandemic trends.The principal drivers of the health outcomes are the fitted values for the overall transmission scaling parameter and disease natural history parameters from other studies, particularly age-specific probabilities of infection and symptomatic disease, as well as social contact rates. Other parameters are investigated in sensitivity analyses.This study is limited by model approximations, available data, and future uncertainty. Because the model is a single-population compartmental model, detailed impacts of nonpharmaceutical interventions (NPIs) such as household isolation cannot be practically represented or evaluated in combination with vaccine programmes. Similarly, the model cannot consider prioritising groups like healthcare or other essential workers. The model is only fitted to the reported case and death data, which are incomplete and not disaggregated by, e.g., age. Finally, because the future impact and implementation cost of NPIs are uncertain, how these would interact with vaccination remains an open question.ConclusionsCOVID-19 vaccination can have a considerable health impact and is likely to be cost-effective if more optimistic vaccine scenarios apply. Preventing severe disease is an important contributor to this impact. However, the advantage of prioritising older, high-risk populations is smaller in generally younger populations. This reduction is especially true in populations with more past transmission, and if the vaccine is likely to further impede transmission rather than just disease. Those conditions are typical of many low- and middle-income countries.

In a modelling study, Carl A B Pearson and coauthors investigate the health impact and cost-effectiveness of various COVID-19 vaccination scenarios in Sindh Province, Pakistan     

Economic impact of dengue illness and the cost-effectiveness of future vaccination programs in Singapore

Background

Dengue illness causes 50–100 million infections worldwide and threatens 2.5 billion people in the tropical and subtropical regions. Little is known about the disease burden and economic impact of dengue in higher resourced countries or the cost-effectiveness of potential dengue vaccines in such settings.

Methods and Findings

We estimate the direct and indirect costs of dengue from hospitalized and ambulatory cases in Singapore. We consider inter alia the impacts of dengue on the economy using the human-capital and the friction cost methods. Disease burden was estimated using disability-adjusted life years (DALYs) and the cost-effectiveness of a potential vaccine program was evaluated. The average economic impact of dengue illness in Singapore from 2000 to 2009 in constant 2010 US$ ranged between $0.85 billion and $1.15 billion, of which control costs constitute 42%–59%. Using empirically derived disability weights, we estimated an annual average disease burden of 9–14 DALYs per 100 000 habitants, making it comparable to diseases such as hepatitis B or syphilis. The proportion of symptomatic dengue cases detected by the national surveillance system was estimated to be low, and to decrease with age. Under population projections by the United Nations, the price per dose threshold for which vaccines stop being more cost-effective than the current vector control program ranged from $50 for mass vaccination requiring 3 doses and only conferring 10 years of immunity to $300 for vaccination requiring 2 doses and conferring lifetime immunity. The thresholds for these vaccine programs to not be cost-effective for Singapore were $100 and $500 per dose respectively.

Conclusions

Dengue illness presents a serious economic and disease burden in Singapore. Dengue vaccines are expected to be cost-effective if reasonably low prices are adopted and will help to reduce the economic and disease burden of dengue in Singapore substantially.     

The cost-effectiveness and value of information of three influenza vaccination dosing strategies for individuals with human immunodeficiency virus

Background

Influenza vaccine immunogenicity is diminished in patients living with HIV/AIDS. We evaluated the cost-effectiveness and expected value of perfect information (EVPI) of three alternative influenza vaccine dosing strategies intended to increase immunogenicity in those patients.

Methods

A randomized, multi-centered, controlled, vaccine trial was conducted at 12 CIHR Canadian HIV Trials Network sites. Three dosing strategies with seasonal, inactivated trivalent, non-adjuvanted intramuscular vaccine were used in HIV infected adults: two standard doses over 28 days (Strategy A), two double doses over 28 days (Strategy B) and a single standard dose of influenza vaccine (Strategy C), administered prior to the 2008 influenza season. The comparator in our analysis was practice in the previous year, in which 82.8% of HIV/AIDS received standard-dose vaccination (Strategy D). A Markov cohort model was developed to estimate the monthly probability of Influenza-like Illness (ILI) over one influenza season. Costs and quality-adjusted life years, extrapolated to the lifetime of the hypothetical study cohorts, were estimated in calculating incremental cost-effectiveness ratios (ICER) and EVPI in conducting further research.

Results

298 patients with median CD4 of 470 cells/µl and 76% with viral load suppression were randomized. Strategy C was the most cost-effective strategy for the overall trial population and for suppressed and unsuppressed individuals. Mean ICERs for Strategy A for unsuppressed patients could also be considered cost-effective. The level of uncertainty regarding the decision to implement strategy A versus C for unsuppressed individuals was high. The maximum acceptable cost of reducing decision uncertainty in implementing strategy A for individuals with unsuppressed pVL was $418,000 - below the cost of conducting a larger-scale trial.

Conclusion

Our results do not support a policy to implement increased antigen dose or booster dosing strategies with seasonal, inactivated trivalent, non-adjuvanted intramuscular vaccine for individuals with HIV in Canada.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00764998","term_id":"NCT00764998"}}NCT00764998.     

The population impact of a large school-based influenza vaccination campaign

Background

The optimal vaccination strategy to mitigate the impact of influenza epidemics is unclear. In 2005, a countywide school-based influenza vaccination campaign was launched in Knox County, Tennessee (population 385,899). Approximately 41% and 48% of eligible county children aged 5–17 years were immunized with live attenuated influenza vaccine before the 2005–2006 and 2006–2007 influenza seasons, respectively. We sought to determine the population impact of this campaign.

Methods

Laboratory-confirmed influenza data defined influenza seasons. We calculated the incidence of medically attended acute respiratory illness attributable to influenza in Knox and Knox-surrounding counties (concurrent controls) during consecutive seasons (5 precampaign and 2 campaign seasons) using negative binomial regression and rate difference methods. Age-stratified analyses compared the incidence of emergency department (ED) visits and hospitalizations attributable to influenza.

Results

During precampaign seasons, estimated ED visit rates attributable to influenza were 12.39 (95% CI: 10.34–14.44) per 1000 Knox children aged 5–17 years and similar in Knox-surrounding counties. During the campaign seasons, annual Knox influenza-associated ED visit rates declined relative to rates in Knox-surrounding counties: rate ratios 0.55 (95% CI: 0.27–0.83) and 0.70 (95% CI: 0.56–0.84) for the first and second campaign seasons, respectively. Overall, there were about 35% or 4.86 per 1000 fewer influenza-associated ED visits among Knox County children aged 5–17 years attributable to the campaign. No significant declines in Knox compared to surrounding counties were detected for influenza associated ED visits in children aged <5 years, all adults combined or selected adult age subgroups, although power for these analyses was limited. Alternate rate-difference analyses yielded consistent results.

Conclusion

Vaccination of approximately 45% of Knox school-aged children with influenza vaccine was associated with a 35% annual reduction (4.86 per 1000) in ED visit rates attributable to influenza. Higher vaccination coverage and/or larger studies would be needed to determine whether similar interventions have indirect benefits in other age groups.     

Individual and collective considerations in public health: influenza vaccination in nursing homes

Many nursing homes have an influenza vaccination policy in which it is assumed that express (proxy) consent is not necessary. Tacit consent procedures are more efficient if one aims at high vaccination rates. In this paper I focus on incompetent residents and proxy consent. Tacit proxy consent for vaccination implies a deviance of standard proxy consent requirements. I analyse several arguments that may possibly support such a deviance. The primary reason to offer influenza vaccination is that vaccinated persons have a significantly reduced risk of getting the flu. This reason however cannot support the assumption that each nursing home resident is 'better off ' if she is vaccinated. Neither can it support tacit proxy consent policies. More promising are arguments that take the collective nature of infectious diseases into account. A potentially strong, but ultimately insufficient, argument for non-express consent is that vaccination contributes to prevention of harm to others. Other arguments emphasise the importance of group protection: herd immunity. I discuss three collective reasons for aiming at herd immunity: solidarity, a common interest in reducing the risk of illness, and a common interest in the prevention of an influenza outbreak. The latter argument appears to be most important. An outbreak is not just detrimental to the health of residents; it is detrimental to their everyday social life as well. Outbreaks can be seen as a collective evil. My analysis shows that there are valid (though not necessarily sufficient) moral arguments for a tacit proxy consent policy.     

Effect of influenza vaccination in patients with asthma

BACKGROUND:Although annual influenza vaccination is recommended for persons with asthma, its effectiveness in this patient population is not well described. We evaluated the effect of influenza vaccination in the current and previous seasons in preventing influenza among people with asthma.METHODS:Using population health data from the Navarre region of Spain for the 2015/16 to 2019/20 influenza seasons, we conducted a test-negative case–control study to assess the effect of influenza vaccination in the current and 5 previous seasons. From patients presenting to hospitals and primary health care centres with influenza-like illness who underwent testing for influenza, we estimated the effects of influenza vaccination among patients with asthma overall and between those presenting as inpatients or outpatients, as well as between patients with and without asthma.RESULTS:Of 1032 patients who had asthma and were tested, we confirmed that 421 had influenza and the remaining 611 were test-negative controls. We found that the average effect of influenza vaccination was 43% (adjusted odds ratio [OR] 0.57, 95% confidence interval [CI] 0.40 to 0.80) for current-season vaccination regardless of previous doses, and 38% (adjusted OR 0.62, 95% CI 0.39 to 0.96) for vaccination in previous seasons only. Effects were similar for outpatients and inpatients. Among patients with asthma and confirmed influenza, current-season vaccination did not reduce the odds of hospital admission (adjusted OR 1.05, 95% CI 0.51 to 2.18). Influenza vaccination effects were similar for patients with and without asthma.INTERPRETATION:We estimated that, on average, current or previous influenza vaccination of people with asthma prevented almost half of influenza cases. These results support recommendations that people with asthma receive influenza vaccination.

Influenza can lead to serious complications in people with risk factors, and the main preventive measure is vaccination. ¹ Influenza infection can exacerbate symptoms of asthma. Because people with asthma have an increased risk of severe complications and hospital admission when infected with influenza virus,^2–5 annual influenza vaccination is recommended worldwide for people with asthma.^1,5–8People who are targeted for influenza vaccination frequently accumulate several doses over successive years,⁹ and adherence to influenza vaccination has been found to be higher in those with asthma.¹⁰ Patients with asthma frequently receive long-term corticosteroid treatment (inhaled or oral), therefore, their systemic immunity may have a reduced response to vaccines.^5,11,12Effectiveness of influenza vaccines in preventing primary health care consultations or hospital admissions in people with asthma has been evaluated in observational studies,^13–15 but we are unaware of any studies that compared the effect in preventing outpatient and inpatient cases or assessed the effect of vaccination in previous seasons.^13,16 The test-negative design is the suggested method to evaluate effectiveness of influenza vaccines in preventing laboratory-confirmed influenza, because it achieves good comparability and control of bias.^17–19 Only 1 study used this method for people with asthma over several seasons.¹³ The pooled analysis of several seasons, the inclusion of inpatients and outpatients, and consideration of vaccination history would provide a complete view of the effect of influenza vaccination in people with asthma.Our objective was to assess the average effect of influenza vaccination status in the current and previous seasons on preventing laboratory-confirmed influenza among people with asthma. We also aimed to compare these estimates with those of the target population for influenza vaccination.     

A model for influenza with vaccination and antiviral treatment

Compartmental models for influenza that include control by vaccination and antiviral treatment are formulated. Analytic expressions for the basic reproduction number, control reproduction number and the final size of the epidemic are derived for this general class of disease transmission models. Sensitivity and uncertainty analyses of the dependence of the control reproduction number on the parameters of the model give a comparison of the various intervention strategies. Numerical computations of the deterministic models are compared with those of recent stochastic simulation influenza models. Predictions of the deterministic compartmental models are in general agreement with those of the stochastic simulation models.     

Fighting misconceptions to improve compliance with influenza vaccination among health care workers: an educational project

The compliance with influenza vaccination is poor among health care workers (HCWs) due to misconceptions about safety and effectiveness of influenza vaccine. We proposed an educational prospective study to demonstrate to HCWs that influenza vaccine is safe and that other respiratory viruses (RV) are the cause of respiratory symptoms in the months following influenza vaccination. 398 HCWs were surveyed for adverse events (AE) occurring within 48 h of vaccination. AE were reported by 30% of the HCWs. No severe AE was observed. A subset of 337 HCWs was followed up during four months, twice a week, for the detection of respiratory symptoms. RV was diagnosed by direct immunofluorescent assay (DFA) and real time PCR in symptomatic HCWs. Influenza A was detected in five episodes of respiratory symptoms (5.3%) and other RV in 26 (27.9%) episodes. The incidence density of influenza and other RV was 4.3 and 10.8 episodes per 100 HCW-month, respectively. The educational nature of the present study may persuade HCWs to develop a more positive attitude to influenza vaccination.     

The social network around influenza vaccination in health care workers: a cross-sectional study

Background

Influenza vaccination coverage remains low among health care workers (HCWs) in many health facilities. This study describes the social network defined by HCWs’ conversations around an influenza vaccination campaign in order to describe the role played by vaccination behavior and other HCW characteristics in the configuration of the links among subjects.

Methods

This study used cross-sectional data from 235 HCWs interviewed after the 2010/2011 influenza vaccination campaign at the Hospital Clinic of Barcelona (HCB), Spain. The study asked: “Who did you talk to or share some activity with respect to the seasonal vaccination campaign?” Variables studied included sociodemographic characteristics and reported conversations among HCWs during the influenza campaign. Exponential random graph models (ERGM) were used to assess the role of shared characteristics (homophily) and individual characteristics in the social network around the influenza vaccination campaign.

Results

Links were more likely between HCWs who shared the same professional category (OR 3.13, 95% CI?=?2.61–3.75), sex (OR 1.34, 95% CI?=?1.09–1.62), age (OR 0.7, 95% CI?=?0.63–0.78 per decade of difference), and department (OR 11.35, 95% CI?=?8.17–15.64), but not between HCWs who shared the same vaccination behavior (OR 1.02, 95% CI?=?0.86–1.22). Older (OR 1.26, 95% CI?=?1.14–1.39 per extra decade of HCW) and vaccinated (OR 1.32, 95% CI?=?1.09–1.62) HCWs were more likely to be named.

Conclusions

This study finds that there is no homophily by vaccination status in whom HCWs speak to or interact with about a workplace vaccination promotion campaign. This result highlights the relevance of social network analysis in the planning of health promotion interventions.

     

Effect of expanded US recommendations for seasonal influenza vaccination: comparison of two pediatric emergency departments in the United States and Canada

Background:

Starting in the 2006/2007 influenza season, the US Advisory Committee on Immunization Practices expanded its recommendations for seasonal influenza vaccination to include healthy children aged 24–59 months. The parallel Canadian organization, the National Advisory Committee on Immunization, did not at that time issue a similar recommendation, thereby creating a natural experiment to evaluate the effect of the policy in the United States.

Methods:

We examined data for 2000/2001 through 2008/2009 and estimated relative changes in visits to the emergency department for influenza-like illness at two pediatric hospitals, one in Boston, Massachusetts, and the other in Montréal, Quebec, following the US policy change. Models were adjusted for virologic factors, seasonal trends and all-cause utilization of the emergency department.

Results:

Of 1 043 989 visits to the emergency departments of the two hospitals for any reason during the study period, 114 657 visits were related to influenza-like illness. Adjusted models estimated a 34% decline in rates of influenza-like illness among children two to four years old in the US hospital relative to the Canadian hospital (rate ratio 0.66, 95% confidence interval 0.58–0.75) following the 2006 policy change of the Advisory Committee on Immunization Practices. This was accompanied by more modest declines of 11% to 18% for the other age groups studied.

Interpretation:

The divergence in influenza rates among children in the US and Canadian sample populations after institution of the US policy to vaccinate children two to four years of age is evidence that the recommendation of the US Advisory Committee on Immunization Practices resulted in a reduction in influenza-related morbidity in the target group and may have indirectly affected other pediatric age groups. Provincial adoption of the 2010 recommendation of teh National Advisory Committee on Immunization in Canada to vaccinate childen two to four years of age might positively affect influenza morbidity in Canada.Seasonal influenza is an important cause of visits to the emergency department among children during winter months, and its control and prevention rely on annual vaccination.^1–4 In the United States, the Advisory Committee on Immunization Practices is responsible for guiding immunization practices, and it revises its recommendations annually. Until the 2004/2005 influenza season, vaccination was targeted to primarily older individuals and those with certain medical conditions.⁵ On the basis of evidence that young children are at elevated risk for admission to hospital because of influenza-related complications, the recommendations were expanded for the 2004/2005 season to include healthy children aged 6–23 months.⁶Starting in the 2006/2007 season, the recommendations of the Advisory Committee on Immunization Practices regarding influenza vaccination were expanded again to include healthy children aged 24–59 months, a shift that added 10.6 million children to the target group.⁷ For the 2008/2009 season, recommendations were further expanded to include all persons 6 months to 18 years old,⁸ and for the 2010/2011 season, the influenza vaccine was advised for all individuals over 6 months of age.⁹In Canada, the National Advisory Committee on Immunization is the federal organization responsible for guiding the use of vaccines. Until the 2006/2007 season, the recommendations of this committee for the use of seasonal influenza vaccines were harmonized with those of its US counterpart. However, it was not until the 2010/2011 season that the Canadian committee began recommending that children two to four years old be routinely vaccinated against influenza, and not all Canadian provinces have adopted this recommendation.We aimed to examine the effect of the 2006 recommendation of the Advisory Committee on Immunization Practices to expand influenza vaccination coverage to preschool-aged children. Interannual variation in severity of disease and effectiveness of the vaccine make it difficult to directly estimate the effect of an intervention on the incidence of influenza in any given community. Instead, we compared surveillance data from the emergency departments of two pediatric hospitals, one in Boston, Massachusetts, and the other in Montréal, Quebec, cities with similar epidemiologic dynamics for seasonal influenza.¹⁰ Our specific objective was to estimate the relative effect of the 2006 US recommendation on influenza-related emergency department visits to Children’s Hospital Boston, with the Montreal Children’s Hospital as an untreated control.     

Potential impact and cost-effectiveness of multi-biofortified rice in China

Biofortification, that is, improving the micronutrient content of staple foods through crop breeding, could be a pro-poor, pro-rural, agriculture-based intervention to reduce the health burden of micronutrient malnutrition. While the potential cost-effectiveness of crops biofortified with single micronutrients was shown in previous research, poor people often suffer from multiple micronutrient deficiencies, which should be accounted for in biofortification initiatives. This study is the first to estimate the potential health benefits and cost-effectiveness of multi-biofortification. Rice with enhanced provitamin A, zinc, iron and folate concentrations is used as a concrete example. The research is conducted for China, the largest rice producer in the world, where micronutrient malnutrition remains a major public health problem. Using the DALY (disability-adjusted life year) framework, the current annual health burden of the four micronutrient deficiencies in China is estimated at 10.6 million DALYs. Introducing multi-biofortified rice could lower this burden by up to 46%. Given the large positive health impact and low recurrent costs of multi-biofortification, this intervention could be very cost effective: under optimistic assumptions, the cost per DALY saved would be around US$ 2; it would stay below US$ 10 even under pessimistic assumptions.     

Effect of vaccination against pneumococcal infection and influenza in children with asthma

Assessment of clinical course of asthma and IgG response in children with asthma immunized with pneumococcal polysaccharide vaccine (Pneumo 23) and influenza vaccine (Vaxigrip). 78 children aged 4 - 17 years old were allocated to two groups. Children from the 1st group were immunized against pneumococcal infection and influenza; children from 2nd group were immunized against pneumococcal infection only. Rate of asthma exacerbations in the 1st group of children decreased by 1.7 times compared with the period before vaccination, whereas the same rate in the 2nd group of children decreased by 1.5 times. It was accompanied by the increase of IgG level to antigens of pneumococcalvaccine in blood, which was observed in both groups. Vaccination did not result in increase of IgE levels. Immunization of children with asthma against pneumococcal infection with polysaccharide vaccine or combined immunization against pneumococcal infection and influenza reduced rate of asthma exacerbations and led to formation of immunity to vaccine strains of Streptococcus pneumoniae. Vaccination did not lead to sensitization of children.