Patterns of emergency room visits, admissions and death following recommended pediatric vaccinations - a population based study of 969,519 vaccination events

Background

The risk of immediate adverse events due to the inflammation created by a vaccine is a potential concern for pediatric vaccine programs.

Methods

We analyzed data on children born between March 2006 and March 2009 in the province of Ontario. Using the self-controlled case series design, we examined the risk of the combined endpoint of emergency room visit and hospital admission in the immediate 3 days post vaccination to a control period 9-18 days after vaccination. We examined the end points of emergency room visits, hospital admissions and death separately as secondary outcomes.

Results

We examined 969,519 separate vaccination events. The relative incidence of our combined end point was 0.85 (0.80-0.90) for vaccination at age 2 months, 0.74 (0.69-0.79) at age 4 months and 0.68 (0.63-0.72) at age 6 months. The relative incidence was reduced for the individual endpoints of emergency room visits, admissions and death. There were 5 or fewer deaths in the risk interval of all 969,519 vaccination events. In a post hoc analysis we observed a large reduction in events in the immediate 3 days prior to vaccination suggesting a large healthy vaccinee effect.

Conclusion

There was no increased incidence of the combined end point of emergency room visits and hospitalizations in the 3-day period immediately following vaccination, nor for individual endpoints or death. The health vaccinee effect could create the perception of worsening health following vaccines in the absence of any vaccine adverse effect and could also mask an effect in the immediate post-vaccination period.     

The Situational Fatigue Scale: A different approach to measuring fatigue

Fatigue can be defined as a subjective state of an imbalance in the availability of inner resources needed to perform physical or mental activities. The level of fatigue is determined not only by the availability of inner resources but also by the demands of the activities performed. Most conventional fatigue scales require subjects to rate their level of fatigue without specifying the situation. In the present study, we constructed a subjective rating scale, the Situational Fatigue Scale (SFS), with which subjects estimated their level of fatigue in specific activities of daily life. We administered the SFS, along with the Fatigue Assessment Instrument (FAI) to 96 outpatients in a family-medicine clinic and to 62 college students to assess the psychometric properties of the SFS. Principle component analysis revealed two underlying factors: physical fatigue and mental fatigue. SFS scores were significantly correlated with several FAI scores and differentiated patients complaining of fatigue from those who did not. The SFS also showed good internal consistency and test–retest reliability. These results suggest that the SFS could be a useful tool to measure a different dimension of the broad concept of fatigue.     

Influenza and pneumococcal vaccination and risk of stroke or transient ischaemic attack—Matched case control study

Background

Evidence that respiratory infections trigger stroke suggests that influenza or pneumococcal vaccination might prevent stroke. We aimed to investigate whether influenza or pneumococcal vaccination or both together were associated with reduced risk of stroke or transient ischaemic attack (TIA).

Methods

We used a matched 1:1 case-control design with data from the United Kingdom General Practice Research Database. Cases, aged 18 years or above with stroke (fatal or non-fatal) and TIA during September 2001 to August 2009, were compared with controls matched for age, sex, calendar time and practice, adjusting for cardiovascular risk factors, vaccine risk groups, comorbidity and indicators of functional ability.

Results

We included 26,784 cases of stroke and 20,227 cases of TIA with equal numbers of matched controls. Influenza vaccination within-season was associated with 24% reduction in stroke risk (adjusted OR 0.76, 95% CI 0.72 to 0.80) but no reduction in TIA (1.03, 0.98 to 1.09). Stroke risk was significantly lower with early (September to mid-November: 0.74, 0.70 to 0.78) but not later influenza vaccination (mid-November onwards: 0.92, 0.83 to 1.01). Associations persisted after multiple imputation of missing data and sensitivity analysis for unmeasured confounders. Pneumococcal vaccination was not associated with a reduction in risk of stroke (0.98, 0.94 to 1.00) or TIA (1.15, 1.08 to 1.23).

Conclusions

Influenza vaccination was associated with a 24% reduction in risk of stroke but not TIA. Pneumococcal vaccination was not associated with reduced risk of stroke or TIA. This has important implications for potential benefits of influenza vaccine.     

E-health use, vaccination knowledge and perception of own risk: drivers of vaccination uptake in medical students

Objective

was to improve understanding of mechanisms contributing to healthcare personnel's (HCP) reluctance to get vaccinated against seasonal influenza. We assessed the role of several drivers: vaccination knowledge, vaccination recommendations and the role of the Internet (so-called e-health) in creating vaccination knowledge. The key mechanism under consideration was the perceived own risk (regarding disease and the vaccine).

Method

310 medical students at the Frankfurt University Hospital answered an anonymous questionnaire assessing risk perceptions, intentions to get vaccinated, knowledge, preferences regarding information sources for personal health decisions and search-terms that they would use in a Google-search directed at seasonal influenza vaccination.

Results

The key driver of vaccination intentions was the perceived own risk (of contracting influenza and of suffering from vaccine adverse events). The recommendation to get vaccinated was a significant, yet weaker predictor. As an indirect driver we identified one's knowledge concerning vaccination. 32% of the knowledge questions were answered incorrectly or as don’t know. 64% of the students were e-health users; therefore, additional information search via the Internet was likely. An analysis of the websites obtained by googling the search-terms provided by the students revealed 30% commercial e-health websites, 11% anti-vaccination websites and 10% public health websites. Explicit searches for vaccination risks led to fewer public health websites than searches without risk as a search term. Content analysis of the first three websites obtained revealed correct information regarding the questions of whether the doses of vaccine additives were dangerous, whether chronic diseases are triggered by vaccines and whether vaccines promote allergies in 58%, 53% and 34% of the websites, respectively. These questions were especially related to own risk, which strongly predicted intentions. Correct information on vaccination recommendations were provided on 85% of the websites.

Conclusion

Concentrating on the key drivers in early medical education (own risk of contracting influenza, vaccine safety, vaccination recommendation) promises to be a successful combination to increase vaccination uptake in HCP.     

Association of influenza vaccination during pregnancy with birth outcomes in Nicaragua

Background: Studies have shown that influenza vaccination during pregnancy reduces the risk of influenza disease in pregnant women and their offspring. Some have proposed that maternal vaccination may also have beneficial effects on birth outcomes. In 2014, we conducted an observational study to test this hypothesis using data from two large hospitals in Managua, Nicaragua.Methods: We conducted a retrospective cohort study to evaluate associations between influenza vaccination and birth outcomes. We carried out interviews and reviewed medical records post-partum to collect data on demographics, influenza vaccination during pregnancy, birth outcomes and other risk factors associated with adverse neonatal outcomes. We used influenza surveillance data to adjust for timing of influenza circulation. We assessed self-reports of influenza vaccination status by further reviewing medical records of those who self-reported but did not have readily available evidence of vaccination status. We performed multiple logistic regression (MLR) and propensity score matching (PSM).Results: A total of 3268 women were included in the final analysis. Of these, 55% had received influenza vaccination in 2014. Overall, we did not observe statistically significant associations between influenza vaccination and birth outcomes after adjusting for risk factors, with either MLR or PSM. With PSM, after adjusting for risk factors, we observed protective associations between influenza vaccination in the second and third trimester and preterm birth (aOR: 0.87; 95% confidence interval (CI): 0.75–0.99 and aOR: 0.66; 95% CI: 0.45–0.96, respectively) and between influenza vaccination in the second trimester and low birth weight (aOR: 0.80; 95% CI: 0.64–0.97).Conclusions: We found evidence to support an association between influenza vaccination and birth outcomes by trimester of receipt with data from an urban population in Nicaragua. The study had significant selection and recall biases. Prospective studies are needed to minimize these biases.     

Trajectories and individual determinants of repeated seasonal flu vaccination use over the long term using data from the French E3N cohort

Despite the implementation of incentive policies to promote seasonal flu vaccination for more than 20 years in France, the coverage of high-risk individuals remains largely insufficient. While there is extensive literature on the determinants of vaccination in a given year, it rarely considers the specificity of flu vaccination, which must be repeated every autumn to remain effective. We aim to fill this gap by focusing on the flu vaccination behavior of high-risk individuals (65 years and older, chronic diseases) over a 15-year period. Based on data from 87,820 women in the French E3N cohort, we used sequence analysis methods (localized Optimal Matching) to identify typical seasonal flu vaccination profiles based on individual trajectories from 2004 to 2018. Then, using a multinomial model, we studied the individual determinants associated with the different patterns of vaccination use identified. Sequence analysis resulted in a partition of 8 clusters, which can be summarized into 4 typical behaviors: almost half of the women get vaccinated against flu each year (43%); conversely, another important share never get vaccinated against flu (32%); some do not get vaccinated for several years and then get vaccinated every year (20%); and finally, a minor share discontinued vaccination (5%). Thus, once women start getting vaccinated they generally continue every year. Nonetheless, this is a double-edged sword, as an important share of women considered at risk refrain from being vaccinated for more than a decade. Determinants associated with regular vaccination are being more at risk (age, weight, and chronic diseases), being in contact with physicians, being more educated, being in couple, having children, not smoking, and undergoing breast cancer screening.     

Simulated computerized adaptive test for patients with shoulder impairments was efficient and produced valid measures of function

BACKGROUND AND OBJECTIVE: To test unidimensionality and local independence of a set of shoulder functional status (SFS) items, develop a computerized adaptive test (CAT) of the items using a rating scale item response theory model (RSM), and compare discriminant validity of measures generated using all items (theta(IRT)) and measures generated using the simulated CAT (theta(CAT)). STUDY DESIGN AND SETTING: We performed a secondary analysis of data collected prospectively during rehabilitation of 400 patients with shoulder impairments who completed 60 SFS items. RESULTS: Factor analytic techniques supported that the 42 SFS items formed a unidimensional scale and were locally independent. Except for five items, which were deleted, the RSM fit the data well. The remaining 37 SFS items were used to generate the CAT. On average, 6 items were needed to estimate precise measures of function using the SFS CAT, compared with all 37 SFS items. The theta(IRT) and theta(CAT) measures were highly correlated (r = .96) and resulted in similar classifications of patients. CONCLUSION: The simulated SFS CAT was efficient and produced precise, clinically relevant measures of functional status with good discriminating ability.     

A case-control study of BCG and childhood tuberculosis in Cali, Colombia

We conducted a case-control study to evaluate the effectiveness of BCG vaccination in preventing childhood tuberculosis (TB) in Cali, Colombia. We ascertained 178 cases aged 0 to 14 years from the respiratory clinics with cough or fever for at least three weeks and a positive chest X-ray for TB, as well as 320 controls who were from the same households but had no symptoms and negative X-rays. Using matched set multiple logistic regression analysis, we found the age- and sex-adjusted relative risk (RR) of TB among vaccinees compared with non-vaccinees to be 0.84 with 95% confidence limits (CL) from 0.43 to 1.62. There was, however, a significantly lowered relative risk of TB with increasing time since vaccination (RR = 0.83 per year since time of vaccination with 95% CL from 0.74 to 0.94.)     

HACCP在预防接种工作中的应用

〔目的〕通过引用危害分析和关键控制点(HACCP)原理,对预防接种过程中潜在的风险及危害性进行分析、识别并采取有效措施加以控制,保障预防接种工作安全。〔方法〕应用危害分析和关键控制点的原理,针对预防接种工作过程中潜在的风险及危害性进行分析研究;根据风险及危害程度识别监测和监视的关键点,并采取有效措施予以控制。〔结果〕实际工作中须严格把握3个关键点即:疫苗质量关,接种操作关,与受种者的沟通。〔结论〕在预防接种工作中实施HACCP,对保障接种的安全具有重要意义。     

The cost-effectiveness of a modestly effective HIV vaccine in the United States

Background

The recent RV144 clinical trial showed that an ALVAC/AIDSVAX prime-boost HIV vaccine regimen may confer partial immunity in recipients and reduce transmission by 31%. Trial data suggest that efficacy may initially exceed 70% but decline over the following 3.5 years. Estimating the potential health benefits associated with a one-time vaccination campaign, as well as the projected benefits of repeat booster vaccination, may inform future HIV vaccine research and licensing decisions.

Methods

We developed a mathematical model to project the future course of the HIV epidemic in the United States under varying HIV vaccine scenarios. The model accounts for disease progression, infection transmission, antiretroviral therapy, and HIV-related morbidity and mortality. We projected HIV prevalence and incidence over time in multiple risk groups, and we estimated quality-adjusted life years (QALYs) and costs over a 10-year time horizon. We assumed an exponentially declining efficacy curve fit to trial data, and that subsequent vaccine boosters confer similar immunity. Variations in vaccine parameters were examined in sensitivity analysis.

Results

Under existing HIV prevention and treatment efforts, an estimated 590,000 HIV infections occur over 10 years. One-time vaccination achieving 60% coverage of adults could prevent 9.8% of projected new infections over 10 years (and prevent 34% of new infections in the first year) and cost approximately $91,000/QALY gained relative to the status quo, assuming $500 per vaccination series. Targeted vaccination strategies result in net cost savings for vaccines costing less than $750. One-time vaccination of 60% of all adults coupled with three-year boosters only for men who have sex with men and people who inject drugs could prevent 21% of infections for $81,000/QALY gained relative to vaccination of higher risk sub-populations only. A program attaining 90% vaccination coverage prevents 15% of new HIV cases over 10 years (and approximately 50% of infections in the first year).

Conclusions

A partially effective HIV vaccine with effectiveness similar to that observed in the RV144 trial would provide large health benefits in the United States and could meet conventionally accepted cost-effectiveness thresholds. Strategies that prioritize key populations are most efficient, but broader strategies provide greater total population health benefit.     

Economic analysis of measles elimination program in the Republic of Korea, 2001: A cost benefit analysis study

Background

In this study, we modeled the cost benefit analysis for three different measles vaccination strategies based upon three different measles-containing vaccines in Korea, 2001. We employed an economic analysis model using vaccination coverage data and population-based measles surveillance data, along with available estimates of the costs for the different strategies. In addition, we have included analysis on benefit of reduction of complication by mumps and rubella.

Methods

We evaluated four different strategies: strategy 1, keep-up program with a second dose measles-mumps-rubella (MMR) vaccine at 4–6 years without catch-up campaign; strategy 2, additional catch-up campaign with measles (M) vaccine; strategy 3, catch-up campaign with measles-rubella (MR) vaccine; and strategy 4, catch-up campaign with MMR vaccine. The cost of vaccination included cost for vaccines, vaccination practices and other administrative expenses. The direct benefit of estimated using data from National Health Insurance Company, a government-operated system that reimburses all medical costs spent on designated illness in Korea.

Results

With the routine one-dose MMR vaccination program, we estimated a baseline of 178,560 measles cases over the 20 years; when the catch-up campaign with M, MR or MMR vaccines was conducted, we estimated the measles cases would decrease to 5936 cases. Among all strategies, the two-dose MMR keep-up program with MR catch-up campaign showed the highest benefit-cost ratio of 1.27 with a net benefit of 51.6 billion KRW.

Conclusion

Across different vaccination strategies, our finding suggest that MR catch-up campaign in conjunction with two-dose MMR keep-up program was the most appropriate option in terms of economic costs and public health effects associated with measles elimination strategy in Korea.     

Factors influencing the durability of hepatitis B vaccine responses

The World Health Organization recommends the implementation of universal hepatitis B (HB) vaccination, and global coverage for this vaccine reached 84% in 2015. In Japan, the policy aimed at preventing mother-to-child transmission of HB virus (HBV) initially commenced as a specific vaccination program for infants born to mothers who were positive for HB surface antigen. In 2016, universal HB vaccination was implemented in this country to cover unvaccinated individuals at risk of horizontal HBV transmission. Although HB vaccination has been shown to be highly efficacious and safe, the issues of vaccine non-responders and of the loss of antibodies directed against HB surface antigen (anti-HBs) in HB vaccine recipients remain. To gain better insight into these problems, we previously performed an immunological analysis on adult vaccine recipients after they received an initial HB vaccination. We found that the course of successful HB vaccination is composed of the following distinct phases: 1) acquisition of anti-HBs antibody, 2) attainment of high anti-HBs antibody titers, and 3) maintenance of acquired anti-HBs antibody levels. In this review, we describe the significance of HB vaccination and suggest a potential means of improving the impact of HB vaccination based on our immunological analysis.     

Influenza vaccination reduces hospitalization for acute coronary syndrome in elderly patients with chronic obstructive pulmonary disease: A population-based cohort study

Background

Elderly patients with chronic obstructive pulmonary disease (COPD) are at a higher risk of hospitalization for cardiovascular complications, especially during respiratory infections. Previous studies showed that vaccination for influenza may reduce the risk of recurrent major cardiovascular events in patients with acute coronary syndrome (ACS). The purpose of this study was to evaluate the hypothesis that influenza vaccination could reduce hospitalizations for ACS in elderly patients with COPD.

Method

Using the Taiwan Longitudinal Health Insurance Database 1996–2008, this cohort study comprised elderly patients (≥55 years old) with a recorded diagnosis of COPD (n = 7722) between January 1, 2000 and December 31, 2007. Each patient was followed until the end of 2007. A propensity score was derived by using a logistic regression model to reduce vaccine therapy selection bias. The hazard ratio (HR) and 95% confidence interval (CI) for the association between the influenza vaccination and the occurrence of first hospitalization for ACS in elderly COPD patients was examined by Cox proportional hazards regression analysis. In addition, we categorized the patients into four groups according to vaccination status (unvaccinated, total number of vaccinations: 1, 2−3, and ≥4).

Results

We found that elderly patients with COPD receiving influenza vaccination had a lower risk of hospitalization for ACS (adjusted HR = 0.46, 95% CI (0.39–0.55), p < 0.001). We observed similar protective effects in both sexes and all age groups (55−64, 65−74, ≥75) regardless of influenza seasonality. When the patients were stratified according to the total number of vaccinations, the adjusted HRs for hospitalization because of ACS were 0.48 (0.38−0.62) and 0.20 (0.14−0.28) for patients who received 2−3 and ≥4 vaccinations during the follow-up period.

Conclusion

Our data showed that there was a lower risk of ACS hospitalization in elderly patients with COPD receiving annual influenza vaccination.     

Clustered lot quality assurance sampling: a tool to monitor immunization coverage rapidly during a national yellow fever and polio vaccination campaign in Cameroon, May 2009

We used the clustered lot quality assurance sampling (clustered-LQAS) technique to identify districts with low immunization coverage and guide mop-up actions during the last 4 days of a combined oral polio vaccine (OPV) and yellow fever (YF) vaccination campaign conducted in Cameroon in May 2009. We monitored 17 pre-selected districts at risk for low coverage. We designed LQAS plans to reject districts with YF vaccination coverage <90% and with OPV coverage <95%. In each lot the sample size was 50 (five clusters of 10) with decision values of 3 for assessing OPV and 7 for YF coverage. We 'rejected' 10 districts for low YF coverage and 14 for low OPV coverage. Hence we recommended a 2-day extension of the campaign. Clustered-LQAS proved to be useful in guiding the campaign vaccination strategy before the completion of the operations.     

Hepatitis B vaccination coverage among high-risk adults 18-49 years, U.S., 2009

Background

Approximately 43,000 new hepatitis B virus (HBV) infections occurred in 2007. Although hepB vaccination has been recommended for adults at high-risk for incident HBV infection for many years, coverage remains low.

Methods

We used the 2009 National Health Interview Survey to assess self-reported HepB vaccine uptake (≥1 dose), series completion (≥3 dose), and independent predictors of vaccination among high-risk adults aged 18-49 years. High-risk adults were defined as those reporting male sex with men; injection drug use; hemophilia with receipt of clotting factors; sexually transmitted disease in prior five years; sex for money or drugs; HIV positive; sex with persons having any above risk factors; or who “felt they were at high risk for HIV”. Persons with none of the aforementioned risk factors were considered non-high risk. Bivariate analysis was conducted to assess vaccination coverage. Independent predictors of vaccine uptake and series completion were determined using a logistic regression.

Results

Overall, 7.0% adults aged 18-49 years had high-risk behaviors. Unadjusted coverage with ≥1 dose was 50.5% among high-risk compared to 40.5% among non-high-risk adults (p-values <0.001) while series completion (≥3 doses) was 41.8% and 34.2%, respectively (p-values <0.001). On multivariable analysis, ≥1 dose coverage, but not series completion, was higher (Risk Ratio 1.1, 95% CI = 1.0-1.2, p-value = 0.021) among high-risk compared to non-high risk adults. Other characteristics independently associated with a higher likelihood of HepB vaccination among persons 18-49 years included younger age groups, females, higher education, ≥2 physician contacts in the past year, ever tested for HIV, health care personnel, received influenza vaccination in the previous year, and ever received hepatitis A vaccination. Vaccine uptake with ≥1 dose increased by 5.1% (p = 0.047) among high-risk adults between 2004 and 2009.

Conclusions

A small increase in ≥1 dose HepB vaccination coverage among high-risk adults compared with non-high risk adults was documented for the first time in 2009. Higher coverage among persons 18-30 years may reflect aging of persons vaccinated when they were children and adolescents. To improve protection against hepatitis B among high-risk adults, healthcare providers should offer hepatitis B vaccination to persons at high risk and those who seek vaccination to protect themselves and facilitate timely completion of the three (3) dose HepB series.     

Spatial and temporal risk as drivers for adoption of foot and mouth disease vaccination

Identifying the drivers of vaccine adoption decisions under varying levels of perceived disease risk and benefit provides insight into what can limit or enhance vaccination uptake. To address the relationship of perceived benefit relative to temporal and spatial risk, we surveyed 432 pastoralist households in northern Tanzania on vaccination for foot-and-mouth disease (FMD). Unlike human health vaccination decisions where beliefs regarding adverse, personal health effects factor heavily into perceived risk, decisions for animal vaccination focus disproportionately on dynamic risks to animal productivity. We extended a commonly used stated preference survey methodology, willingness to pay, to elicit responses for a routine vaccination strategy applied biannually and an emergency strategy applied in reaction to spatially variable, hypothetical outbreaks. Our results show that households place a higher value on vaccination as perceived risk and household capacity to cope with resource constraints increase, but that the episodic and unpredictable spatial and temporal spread of FMD contributes to increased levels of uncertainty regarding the benefit of vaccination. In addition, concerns regarding the performance of the vaccine underlie decisions for both routine and emergency vaccination, indicating a need for within community messaging and documentation of the household and population level benefits of FMD vaccination.     

Guillain-Barré syndrome and H1N1 (2009) pandemic influenza vaccination using an AS03 adjuvanted vaccine in the United Kingdom: self-controlled case series

In 1976 a swine influenza vaccine was associated with an increased risk of Guillain-Barré syndrome (GBS). Although subsequent studies did not find an increased risk of GBS following seasonal influenza vaccine, there was concern that the monovalent H1N1 vaccines developed against the swine influenza pandemic of 2009 might increase the risk of GBS. In the UK a split-virion AS03 oil-in-water adjuvanted vaccine (Pandemrix™) was predominantly used. To determine whether the risk of GBS increased after Pandemrix administration, we sought GBS cases during the period of vaccine use from neurologists and a patient support group, and following the vaccination period from hospital episode statistics (HES) in England. We obtained cases’ vaccination histories and illness onset dates from general practitioners. We determined the relative incidence of GBS in the 6 weeks after vaccination using the self-controlled case series method on the cases identified in HES. We included 327 GBS cases, of whom 37 received pandemic vaccine in the study period, nine of whom developed GBS within 6 weeks of vaccination (relative incidence 1.05 [95% confidence interval (CI) 0.37 to 2.24]). We found no evidence of an increased risk of GBS in the 6 weeks following pandemic influenza vaccination.     

Myocarditis and pericarditis are rare following live viral vaccinations in adults

Reports of myocarditis and pericarditis following smallpox vaccination in adults suggested a need to assess inflammatory cardiac disease risk among adults who receive live viral vaccinations. From 1996 through 2007, among 416,629 vaccinated adults in the Vaccine Safety Datalink, we identified one probable pericarditis case and no cases of myocarditis in the 42 days following a live viral vaccination. Our self-controlled risk interval analysis found that, based on one case identified during the risk interval and 10 cases during the control interval, there is no increased risk of myopericarditis in the 42 days following vaccination (IRR, 0.57; 95% CI, 0.07, 4.51). Our study suggests that the occurrence of myopericarditis following live viral vaccination is rare with an estimated incidence of 0.24 per 100,000 vaccinated, which is not higher than the background rate and is much lower than the incidence rates reported following smallpox vaccination.     

Products formed during fermentation of the prebiotic inulin with human gut flora enhance expression of biotransformation genes in human primary colon cells

Inulin-type fructans are fermented by gut bacteria to yield SCFA, including butyrate which is trophic for colonocytes and induces glutathione S-transferases (GST) that detoxify carcinogens. Since little is known on similar effects by complex fermentation samples, we studied related products in non-transformed human colonocytes. Inulin enriched with oligofructose (1:1, Synergy1) was fermented with human gut flora. SCFA were quantified and a SCFA mixture was prepared accordingly. Colonocytes were incubated (4-12 h) with the Synergy1 fermentation supernatant (SFS), faeces control, a mixture of the three major SCFA (each 0-15 %, v/v) or butyrate (0-50 mM). Metabolic activity was determined to assess trophic effects and cytotoxicity. Expression of ninety-six genes related to biotransformation was studied using cDNA macroarrays. Results on modulated GST were reassessed with real-time PCR and GST activity was measured. Fermentation of inulin resulted in 2-3-fold increases of SCFA. The samples were non-cytotoxic. SFS increased metabolic activity, pointing to trophic effects. The samples modulated gene expression with different response patterns. Key results were that GSTM2 (2.0-fold) and GSTM5 (2.2-fold) were enhanced by SFS, whereas the SCFA mixture reduced expression. The faeces control enhanced GSTA4 (2.0-fold), but reduced GSTM2 (0.2-fold) and GSTM5 (0.2-fold). Realtime qPCR confirmed the induction of GSTM2 and GSTM5 by SFS and of GSTA4 and GSTT2 by butyrate. Activity of GST was not modulated. High concentrations of fermentation products were well tolerated by primary colonocytes, pointing to trophic effects. The induction of GST by the SFS may protect the cells from carcinogenic compounds.     

Effects of geographic and economic heterogeneity on the burden of rotavirus diarrhea and the impact and cost-effectiveness of vaccination in Pakistan

Globally, rotavirus is a leading cause of childhood diarrhea and related mortality. Although rotavirus vaccination has been introduced in many countries worldwide, there are numerous low- to middle-income countries that have not yet introduced. Pakistan is one of the countries with the highest number of rotavirus deaths in children under five years. Although rotavirus infection is almost universal among children, mortality is often a result of poor nutrition and lack of access to health care and other aspects of poverty. We assess the impact and cost-effectiveness of introducing childhood rotavirus vaccination in Pakistan. We use household data from the 2012–2013 Demographic Health survey in Pakistan to estimate heterogeneity in rotavirus mortality risk, vaccination benefits, and cost-effectiveness across geographic and economic groups. We estimate two-dose rotavirus vaccination coverage that would be distributed through a routine vaccination program. In addition, we estimate rotavirus mortality (burden), and other measures of vaccine cost-effectiveness and impact by subpopulations of children aggregated by region and economic status. Results indicate that the highest estimated regional rotavirus burden is in Sindh (3.3 rotavirus deaths/1000 births) and Balochistan (3.1 rotavirus deaths/1000 births), which also have the lowest estimated vaccination coverage, particularly for children living in the poorest households. In Pakistan, introduction could prevent 3061 deaths per year with current routine immunization patterns at an estimated $279/DALY averted. Increases in coverage to match the region with highest coverage (Islamabad) could prevent an additional 1648 deaths per year. Vaccination of children in the highest risk regions could result in a fourfold mortality reduction as compared to low risk children, and children in the poorest households have a three to four times greater mortality reduction benefit than the richest. Based on the analysis presented here, the benefits and cost-effectiveness of rotavirus vaccination can be maximized by reaching economically and geographically vulnerable children.