Seroprevalence and assessment of public awareness of Brucella spp., Toxoplasma gondii and Chlamydia abortus in small ruminants from selected smallholder commercial farms of Zimbabwe.

Brucella spp., Toxoplasma gondii, and Chlamydia abortus have long been recognized as zoonoses and significant causes of reproductive failure in small ruminants globally. A cross-sectional study was conducted in August 2020 to determine the seroprevalences of Brucella spp., Toxoplasma gondii and Chlamydia abortus in 398 small ruminants from four districts of Zimbabwe (Chivi, Makoni, Zvimba, and Goromonzi) using Indirect-ELISAs. A structured questionnaire was used to assess the knowledge, attitudes, and practices of 103 smallholder farmers towards small ruminant abortions, Brucella spp., T. gondii and C. abortus, and to obtain a general overview of the significance of small ruminant reproductive failure(s) on their livelihoods. The overall seroprevalences were: 9.1% (95% CI: 6.4-12.3) for Brucella spp., 6.8% (95% CI: 4.5-9.7) for T. gondii and 2.0% (95% CI: 0.9-3.9) for C. abortus. Location, age, parity, and abortion history were associated with Brucella spp. seropositivity. Location was also associated with both T. gondii and C. abortus seropositivity. The questionnaire survey established that 44% of respondents had recently faced reproductive disease challenges within their flocks, with 34% correctly identifying abortion causes and only 10%, 6% and 4% having specific knowledge of Brucella spp., C. abortus and T. gondii, respectively. This study provides the first serological evidence of Brucella spp. in small ruminants since 1996 and builds the evidence on small ruminant toxoplasmosis and chlamydiosis in Zimbabwe. Evidence of these zoonoses in small ruminants and the paucity of knowledge shows the need for a coordinated One Health approach to increase public awareness of these diseases, and to establish effective surveillance and control measures. Further studies are required to establish the role these diseases play in small ruminant reproductive failure(s), to identify the Brucella spp. detected here to species/subspecies level, and to assess the socio-economic impact of reproductive failure in livestock among marginalised rural communities.

Estimating the health impact of vaccination against ten pathogens in 98 low-income and middle-income countries from 2000 to 2030: a modelling study.

BACKGROUND: The past two decades have seen expansion of childhood vaccination programmes in low-income and middle-income countries (LMICs). We quantify the health impact of these programmes by estimating the deaths and disability-adjusted life-years (DALYs) averted by vaccination against ten pathogens in 98 LMICs between 2000 and 2030. METHODS: 16 independent research groups provided model-based disease burden estimates under a range of vaccination coverage scenarios for ten pathogens: hepatitis B virus, Haemophilus influenzae type B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, Streptococcus pneumoniae, rotavirus, rubella, and yellow fever. Using standardised demographic data and vaccine coverage, the impact of vaccination programmes was determined by comparing model estimates from a no-vaccination counterfactual scenario with those from a reported and projected vaccination scenario. We present deaths and DALYs averted between 2000 and 2030 by calendar year and by annual birth cohort. FINDINGS: We estimate that vaccination of the ten selected pathogens will have averted 69 million (95% credible interval 52-88) deaths between 2000 and 2030, of which 37 million (30-48) were averted between 2000 and 2019. From 2000 to 2019, this represents a 45% (36-58) reduction in deaths compared with the counterfactual scenario of no vaccination. Most of this impact is concentrated in a reduction in mortality among children younger than 5 years (57% reduction [52-66]), most notably from measles. Over the lifetime of birth cohorts born between 2000 and 2030, we predict that 120 million (93-150) deaths will be averted by vaccination, of which 58 million (39-76) are due to measles vaccination and 38 million (25-52) are due to hepatitis B vaccination. We estimate that increases in vaccine coverage and introductions of additional vaccines will result in a 72% (59-81) reduction in lifetime mortality in the 2019 birth cohort. INTERPRETATION: Increases in vaccine coverage and the introduction of new vaccines into LMICs have had a major impact in reducing mortality. These public health gains are predicted to increase in coming decades if progress in increasing coverage is sustained. FUNDING: Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation.

Health impact and cost-effectiveness of introducing the vaccine (Bexsero) against MenB disease into the Brazilian immunization programme.

Invasive meningococcal disease (IMD) is associated with a high mortality and severe sequelae. The aim of the present study was to evaluate the potential cost-effectiveness of the Bexsero vaccine in Brazil. We used a cohort model to compare routine vaccination against MenB disease with no vaccination. Epidemiological and cost estimates were obtained from the Brazilian Health Information System. The cost per disability-adjusted life year (DALY) averted and incremental cost-effectiveness ratio (ICER) was estimated assuming a 3-dose vaccination schedule, at R$90 (£ 20.50) per vaccine dose, 82.0% vaccine efficacy against MenB disease and a vaccine uptake of 90.0%. We estimated that 1,527 MenB cases would be prevented and 78 deaths averted. This strategy would cost R$ 762,381, 000 (£ 174,059,503) with a R$ 4,364,280 (£ 996,410) reduction in disease treatment costs. However, at an ICER of 372,256 (£ 84,990) per DALY averted, a vaccination programme is unlikely to be cost-effective.

The views of the general public on prioritising vaccination programmes against childhood diseases: A qualitative study.

BACKGROUND: Decisions regarding which vaccines are funded in the United Kingdom (UK) are increasingly informed by cost-effectiveness analyses. Such analyses use Quality Adjusted Life Years (QALYs) as a measure of effectiveness and assume that QALYs are equal regardless of where and in whom they occur in the population. However, there is increasing debate about whether this QALY approach is appropriate and whether societal preferences for childhood vaccinations should be used to help inform childhood immunisation policy. OBJECTIVE: To gauge the general public's preferences for prioritising certain characteristics of childhood vaccination, to help inform future policy making decisions in the UK. DESIGN: Qualitative design using individual face-to-face interviews, with data analysed using an inductive thematic framework approach. SETTING: Two counties in England, UK. POPULATION: Adult members of the general public were recruited using the Bristol and South Gloucestershire open electoral registers, using gender and deprivation quotas for each area. PARTICIPANTS: 21 members of the public participated in qualitative interviews. RESULTS: The qualitative research identified three major themes and several key attributes that influences participant's opinions about priority setting for childhood vaccinations: (1) population segment (i.e. age group, carer impact and social group), (2) vaccine preventable diseases preferences (i.e. disease severity, disease incidence and declining infection) and (3) risks and benefits associated with childhood vaccinations (i.e. vaccine associated side-effects, herd protection and peace of mind). CONCLUSION: Evidence from this qualitative study suggests that some members of the UK general public have more nuanced views than the health-maximisation approach when considering how childhood vaccines should be prioritised. This is not necessarily captured by the current economic approaches for assessing the benefits from childhood vaccinations in the UK, but is an important area for future research to ensure appropriate decision making.

Modelling the cost-effectiveness of catch-up 'MenB' (Bexsero) vaccination in England.

We assessed the cost-effectiveness of offering catch-up vaccination with Bexsero against meningococcal disease to children too old to receive the vaccine under the recently introduced infant programme. Offering catch-up vaccination to increasingly older children is less economically attractive because of declining disease burden. We estimate catch-up vaccination of 1year old children could be cost-effective, incremental on the infant programme with a vaccine price of ⩽£8 per dose. Extending vaccination to 2year olds could only be cost-effective (incremental on infant and 1year old catch-up) with a vaccine price of ⩽£3 per dose and was not cost-effective in sensitivity analyses with more conservative vaccine assumptions. Extending catch-up further to 3-4year olds was not cost-effective. Employing the current criteria for assessing vaccines, our models suggest that even with low vaccine prices only catch-up vaccination in 1year old children could be cost-effective, when considered incrementally on the infant programme.

Epidemiological impact and cost-effectiveness of universal vaccination with Bexsero(®) to reduce meningococcal group B disease in Germany.

Bexsero, a new vaccine against serogroup B meningococcal disease (MenB), was licensed in Europe in January 2013. In Germany, Bexsero is recommended for persons at increased risk of invasive meningococcal disease, but not for universal childhood vaccination. To support decision making we adapted the independently developed model for England to the German setting to predict the potential health impact and cost-effectiveness of universal vaccination with Bexsero(®) against MenB disease. We used both cohort and transmission dynamic mathematical models, the latter allowing for herd effects, to consider the impact of vaccination on individuals aged 0-99 years. Vaccination strategies included infant and adolescent vaccination, alone or in combination, and with one-off catch-up programmes. German specific data were used where possible from routine surveillance data and the literature. We assessed the impact of vaccination through cases averted and quality adjusted life years (QALY) gained and calculated costs per QALY gained. Assuming 65% vaccine uptake and 82% strain coverage, infant vaccination was estimated to prevent 15% (34) of MenB cases over the lifetime of one birth cohort. Including herd effects from vaccination increased the cases averted by infant vaccination to 22%, with an estimated 8461 infants requiring vaccination to prevent one case. In the short term the greatest health benefit is achieved through routine infant vaccination with large-scale catch-up, which could reduce cases by 24.9% after 5 years and 27.9% after 10 years. In the long term (20+ years) policies including routine adolescent vaccination are most favourable if herd effects are assumed. Under base case assumptions with a vaccine list price of €96.96 the incremental cost-effectiveness ratio (ICER) was >€500,000 per QALY for all considered strategies. Given the current very low incidence of MenB disease in Germany, universal vaccination with Bexsero(®) would prevent only a small absolute number of cases, at a high overall cost.

Barriers and facilitators to uptake of the school-based HPV vaccination programme in an ethnically diverse group of young women.

BACKGROUND: To identify the barriers and facilitators to uptake of the HPV vaccine in an ethnically diverse group of young women in the south west of England. METHODS: Three school-based vaccination sessions were observed. Twenty-three young women aged 12 to 13 years, and six key informants, were interviewed between October 2012 and July 2013. Data were analysed using thematic analysis and the Framework method for data management. RESULTS: The priority given to preventing cervical cancer in this age group influenced whether young women received the HPV vaccine. Access could be affected by differing levels of commitment by school staff, school nurses, parents and young women to ensure parental consent forms were returned. Beliefs and values, particularly relevant to minority ethnic groups, in relation to adolescent sexual activity may affect uptake. Literacy and language difficulties undermine informed consent and may prevent vaccination. CONCLUSIONS: The school-based HPV vaccination programme successfully reaches the majority of young women. However, responsibility for key aspects remain unresolved which can affect delivery and prevent uptake for some groups. A multi-faceted approach, targeting appropriate levels of the socio-ecological model, is required to address procedures for consent and cultural and literacy barriers faced by minority ethnic groups, increase uptake and reduce inequalities.

Re-evaluating cost effectiveness of universal meningitis vaccination (Bexsero) in England: modelling study.

OBJECTIVE: To use mathematical and economic models to predict the epidemiological and economic impact of vaccination with Bexsero, designed to protect against group B meningococcal disease, to help inform vaccine policy in the United Kingdom. DESIGN: Modelling study. SETTING: England. POPULATION: People aged 0-99. INTERVENTIONS: Incremental impact of introductory vaccine strategies simulated with a transmission dynamic model of meningococcal infection and vaccination including potential herd effects. Model parameters included recent evidence on the vaccine characteristics, disease burden, costs of care, litigation costs, and loss of quality of life from disease, including impacts on family and network members. The health impact of vaccination was assessed through cases averted and quality adjusted life years (QALYs) gained. MAIN OUTCOME MEASURES: Cases averted and cost per QALY gained through vaccination; programmes were deemed cost effective against a willingness to pay of £20,000 (€25,420, $32,677) per QALY gained from an NHS and personal and social services perspective. RESULTS: In the short term, case reduction is greatest with routine infant immunisation (26.3% of cases averted in the first five years). This strategy could be cost effective at £3 (€3.8, $4.9) a vaccine dose, given several favourable assumptions and the use of a quality of life adjustment factor. If the vaccine can disrupt meningococcal transmission more cases are prevented in the long term with an infant and adolescent combined programme (51.8% after 30 years), which could be cost effective at £4 a vaccine dose. Assuming the vaccine reduces acquisition by 30%, adolescent vaccination alone is the most favourable strategy economically, but takes more than 20 years to substantially reduce the number of cases. CONCLUSIONS: Routine infant vaccination is the most effective short term strategy and could be cost effective with a low vaccine price. Critically, if the vaccine reduces carriage acquisition in teenagers, the combination of infant and adolescent vaccination could result in substantial long term reductions in cases and be cost effective with competitive vaccine pricing.

The health, social and educational needs of children who have survived meningitis and septicaemia: the parents' perspective.

BACKGROUND: Survivors of bacterial meningitis and septicaemia can experience a range of after-effects. There is little published research on the needs and provision of aftercare for children surviving bacterial meningitis and septicaemia. METHODS: Mixed methods study employing a survey and follow-up interviews with a sample of survey participants recruited from Meningitis Research Foundation's member database and social media. RESULTS: Of 194 eligible survey respondents, 77% reported at least moderate short-term after-effects, and 57% a need for aftercare or support. Most parents reported that their child received a hearing test (98%) and follow-up appointment with a paediatrician (66%). Psychosocial after-effects were most common and the greatest need was for educational support. About half of participants felt their children's needs for aftercare were met. We conducted interviews with 18 parents. Findings suggest access could be limited by: parents' inability to navigate systems in place, child's age, and delayed identification of sequelae. Parents felt a comprehensive explanation of possible after-effects on discharge from hospital was required, and found uncertain prognoses difficult. Good communication between professionals enabled a service tailored to the child's needs. CONCLUSIONS: Our study supports the NICE and SIGN guidelines and highlights areas for improvement in the aftercare of these children.

Inequalities in the uptake of human papillomavirus vaccination: a systematic review and meta-analysis.

BACKGROUND: The human papillomavirus (HPV) vaccine offers an opportunity to reduce health inequalities associated with cervical cancer provided the vaccine is delivered equitably at population level. Method We reviewed evidence of inequalities in HPV vaccine uptake in young women after undertaking a comprehensive search of databases from inception to March 2012. Studies that compared HPV vaccination initiation and/or completion by at least one ethnicity or socioeconomic-related variable in adolescent young women were included. There were no language restrictions. Data were extracted by two reviewers and pooled in a meta-analysis using a random-effects model; sub-analyses and meta-regression were undertaken to investigate sources of heterogeneity. RESULTS: In all, 29 publications related to 27 studies were included in the review. Black young women were less likely to initiate HPV vaccination compared with White young women (combined OR: 0.89, 95% CI: 0.82-0.97). In the USA, young women without healthcare insurance were less likely to initiate (combined OR: 0.56, 95% CI: 0.40-0.78). There was no strong evidence that lower family income (combined OR: 1.16, 95% CI: 1.00-1.34) or lower parental education (combined OR 1.06, 95% CI: 0.92-1.22) influenced HPV vaccination initiation. CONCLUSIONS: We found strong evidence for differences in HPV vaccination initiation by ethnicity and healthcare coverage, but did not find a strong association with parental education or family income variables. The majority of studies originated from the USA. Population-based studies reporting both initiation and completion of the HPV vaccination programme are required to establish patterns of uptake in different healthcare contexts.

Introducing vaccination against serogroup B meningococcal disease: an economic and mathematical modelling study of potential impact.

BACKGROUND: Meningococcal disease remains an important cause of morbidity and mortality worldwide. The first broadly effective vaccine against group B disease (which causes considerable meningococcal disease in Europe, the Americas and Australasia) was licensed in the EU in January 2013; our objective was to estimate the potential impact of introducing such a vaccine in England. METHODS: We developed two models to estimate the impact of introducing a new 'MenB' vaccine. The cohort model assumes the vaccine protects against disease only; the transmission dynamic model also allows the vaccine to protect against carriage (accounting for herd effects). We used these, and economic models, to estimate the case reduction and cost-effectiveness of a number of different vaccine strategies. RESULTS: We estimate 27% of meningococcal disease cases could be prevented over the lifetime of an English birth cohort by vaccinating infants at 2,3,4 and 12 months of age with a vaccine that prevents disease only; this strategy could be cost-effective at £9 per vaccine dose. Substantial reductions in disease (71%) can be produced after 10 years by routinely vaccinating infants in combination with a large-scale catch-up campaign, using a vaccine which protects against carriage as well as disease; this could be cost-effective at £17 per vaccine dose. CONCLUSIONS: New 'MenB' vaccines could substantially reduce disease in England and be cost-effective if competitively priced, particularly if the vaccines can prevent carriage as well as disease. These results are relevant to other countries, with a similar epidemiology to England, considering the introduction of a new 'MenB' vaccine.

Vaccination of risk groups in England using the 13 valent pneumococcal conjugate vaccine: economic analysis.

OBJECTIVE: To estimate the cost effectiveness of vaccinating people with high risk conditions against invasive pneumococcal disease using the 13 valent pneumococcal conjugate vaccine. DESIGN: Economic evaluation using a cohort model from the perspective of healthcare providers. SETTING: England. PARTICIPANTS: People aged 2 years and older at increased risk of invasive pneumococcal disease due to chronic kidney disease; splenic dysfunction; HIV infection; a compromised immune system; chronic heart, liver, or respiratory disease; or diabetes. MAIN OUTCOME MEASURES: Costs, gains in life years and quality adjusted life years (QALYs), and incremental cost effectiveness ratios. RESULTS: Increasing indirect protection resulting from the vaccination programme of infants using the 13 valent pneumococcal conjugate vaccine means that the burden of disease preventable by targeting high risk groups will diminish in time. Under base case assumptions--that is, no overall impact on non bacteraemic pneumonia in high risk groups and assuming the high risk vaccination programme would be launched two to three years after the infant programme--the incremental cost effectiveness ratio was estimated to be more than £30,000 (€37,216; $48,210) per QALY gained for most risk groups. If, however, the vaccine does not offer protection against non-bacteraemic pneumococcal pneumonia or the vaccine was introduced concomitantly with the infant 13 valent pneumococcal conjugate vaccination programme then vaccinating high risk people would (more) likely be cost effective. Sensitivity analyses showed that the cost effectiveness was particularly sensitive to assumed herd benefits and vaccine efficacy estimates. CONCLUSION: Under base case assumptions it is unlikely that a pneumococcal vaccination programme aimed at risk groups could be considered cost effective. Uncertainty could be substantially reduced by establishing the effectiveness of the 13 valent pneumococcal conjugate vaccine against non-bacteraemic pneumococcal pneumonia, particularly in at risk groups.

Modeling future changes to the meningococcal serogroup C conjugate (MCC) vaccine program in England and Wales.

The UK meningococcal serogroup C conjugate (MCC) vaccine program has successfully controlled serogroup C disease, due to high vaccine effectiveness and substantial herd immunity. However, children immunised at 2, 3 and 4 months of age receive only short-term direct protection and may be at risk of disease 15 months after vaccination. To investigate this we applied a mathematical model to predict the future epidemiology of serogroup C disease, with and without changes to the immunization schedule. Only a few cases of serogroup C disease were predicted to occur over the next few years because of persisting herd immunity, even without a change to the vaccine schedule. The inclusion of a booster dose is likely to improve the impact of the MCC program and reducing the number of doses in infancy will improve cost-effectiveness and create space in the schedule for the addition of other vaccines.

Reassessing the cost-effectiveness of meningococcal serogroup C conjugate (MCC) vaccines using a transmission dynamic model.

BACKGROUND: The meningococcal serogroup C conjugate (MCC) vaccination program has successfully reduced morbidity and mortality from serogroup C disease in England and Wales, owing to high short-term vaccine effectiveness and substantial herd immunity. The latter effect was not accounted for in the previous economic analysis of the MCC program. METHODS: The authors applied a transmission dynamic model, which accounts for herd immunity, to reevaluate the cost-effectiveness of MCC vaccination. The direct and indirect benefits of the MCC vaccine strategy implemented in England and Wales were compared. The cost-effectiveness of alternative MCC vaccine strategies, including future changes to the current schedule, were evaluated. RESULTS: The authors found that including herd immunity improved the average cost-effectiveness ratio in all cases, although the extent depended on the vaccine strategy considered. Incremental analysis showed that those strategies that offered 1 dose early in the 2nd year of life dominated strategies that offered 3 doses of vaccine in infancy and that catch-up vaccination up to the age of 18 years was also highly attractive. Furthermore, the authors analyzed the effect of future changes to the routine vaccine schedule and predicted that shifting the age at routine vaccination from 2, 3, and 4 months (3 doses) to 12 months (1 dose) resulted in a net gain in the total number of cases prevented with only a few extra cases occurring in children under 1 year of age. This program dominated the current strategy. CONCLUSIONS: Models that do not include the indirect effects of vaccination will underestimate the impact of MCC vaccination and may lead to distorted decision making.

The role of economic evaluation in vaccine decision making: focus on meningococcal group C conjugate vaccine.

In recent years, several countries have experienced increases in the incidence of serogroup C meningococcal disease. It can be controlled with older polysaccharide vaccines and particularly the recently developed conjugate vaccines. For 21 developed countries, we investigated the role that economic evaluation played in the decision to introduce the conjugate vaccine into either the routine childhood vaccination schedule, as a mass vaccination 'catch-up' campaign or not at all. A literature review was performed and experts from these countries were contacted. For six countries, we identified published economic evaluations for meningococcal C conjugate vaccination. In four of them (Australia, Canada [Quebec], The Netherlands and the UK) the analyses were performed before a decision about the use of the conjugate vaccine was made. In all of these countries, the economic evaluation offered guidance as to the most efficient way to add the conjugate vaccine to the routine infant immunisation schedule and, in three countries, this advice was adopted by decision makers. In Portugal and Switzerland, initial vaccination decisions were made without the economic evaluations that are influencing current decision making. Of the countries without economic evaluations, six implemented vaccination programmes. Overall, there was a positive correlation between the reported incidence of meningococcal C disease and (a) the decision to vaccinate and (b) performing an economic evaluation. All economic evaluations were modelling studies. The reported cost-effectiveness ratios were sensitive to the age of vaccination, the future meningococcal incidence, vaccine price and some methodological characteristics that varied widely between studies making direct comparisons difficult. In conclusion, in almost all countries where economic evaluations for meningococcal C conjugate vaccinations have been conducted, their results had an important role in the decision-making process. However, in most countries with strongly increasing meningococcal incidence, public health considerations took precedence. In order to improve the international comparability of such studies, firmer national and international modelling guidelines and better adherence to such guidelines seem necessary.

Modelling cost effectiveness of meningococcal serogroup C conjugate vaccination campaign in England and Wales.

OBJECTIVES: To assess the cost effectiveness of a meningococcal serogroup C conjugate vaccination campaign in 0-17 year olds. DESIGN: Cost effectiveness analysis from the perspective of the healthcare provider. SETTING: England and Wales. MAIN OUTCOME MEASURE: Cost per life year saved. RESULTS: In 1998-9, immediately before the introduction of meningococcal C vaccination, the burden of serogroup C disease was considerable, with an estimated 1137 cases in people aged 0-17 years and at least 72 deaths. The vaccination campaign is estimated to have cost between 126m pound sterling ($180m, 207m) and 241 pound sterling 3m, 395m), depending on the price of the vaccine. Under base case assumptions the cost per life year saved from the vaccination campaign is estimated to be 6259 pound sterling. School based vaccination was more cost effective than general practice based vaccination because of lower delivery costs. Immunisation of infants aged under 1 year was the least cost effective component of the campaign because, although this maximises the life years gained, the three dose schedule required is more expensive than other methods of delivery. Estimates of the cost per life year saved were sensitive to assumptions on the future incidence of disease and the case fatality ratio. CONCLUSIONS: Meningococcal C vaccination is likely to be more cost effective in all age groups when the incidence of disease is high. It is also more cost effective when given to children aged 1-4 (by general practitioners) and to children and young people aged 5-17 years at school than when administered to infants under 12 months of age or young people aged 16-17 years who are not at school.