Understanding and explaining the link between anthroposophy and vaccine hesitancy: a systematic review.

BACKGROUND: Due to low vaccination uptake and measles outbreaks across Europe, public health authorities have paid increasing attention to anthroposophic communities. Public media outlets have further described these communities as vaccine refusers or "anti-vaxxers". The aim of this review was to understand the scope of the problem and explore assumptions about vaccination beliefs in anthroposophic communities. For the purpose of this review, we define anthroposophic communities as people following some/certain views more or less loosely connected to the philosophies of anthroposophy. The systematic review addresses three research questions and (1) collates evidence documenting outbreaks linked to anthroposophic communities, (2) literature on vaccination coverage in anthroposophic communities, and (3) lastly describes literature that summarizes theories and factors influencing vaccine decision-making in anthroposophic communities. METHODS: This is a systematic review using the following databases: Medline, Web of Science, Psycinfo, and CINAHL. Double-blinded article screening was conducted by two researchers. Data was summarized to address the research questions. For the qualitative research question the data was analysed using thematic analysis with the assistance of Nvivo12.0. RESULTS: There were 12 articles documenting 18 measles outbreaks linked to anthroposophic communities between the years 2000 and 2012. Seven articles describe lower vaccination uptake in anthroposophic communities than in other communities, although one article describes that vaccination coverage in low-income communities with a migrant background was lower than in the anthroposophic community they studied. We found eight articles examining factors and theories influencing vaccine decision making in anthroposophic communities. The qualitative analysis revealed four common themes. Firstly, there was a very broad spectrum of vaccine beliefs among the anthroposophic communities. Secondly, there was a consistent narrative about problems or concerns with vaccines, including toxicity and lack of trust in the system. Thirdly, there was a strong notion of the importance of making individual and well-informed choices as opposed to simply following the masses. Lastly, making vaccine choices different from public health guidelines was highly stigmatized by those outside of the anthroposophic community but also those within the community. CONCLUSION: Continuing to further knowledge of vaccine beliefs in anthroposophic communities is particularly important in view of increasing measles rates and potential sudden reliance on vaccines for emerging diseases. However, popular assumptions about vaccine beliefs in anthroposophic communities are challenged by the data presented in this systematic review.

Timeliness of childhood vaccination in England: A population-based cohort study.

INTRODUCTION: Vaccine surveillance for children in England focuses on coverage at ages 1, 2, and 5 years. Previous studies exploring vaccine timeliness have used different arbitrary categories to define whether vaccines were received 'late' or 'on time'. This paper aims to provide more detailed and holistic information on timing and patterns of vaccine uptake across the childhood immunisation schedule in England. METHODS: We included all children born in England between 2006 and 2014 and registered in the Clinical Practice Research Datalink (CPRD) Aurum, a primary care electronic health record. We described vaccine uptake for representative antigens (pertussis, pneumococcus, measles) by age in days and stratified by ethnicity, region and birth cohort. Alluvial diagrams were used to illustrate common journeys through the vaccination schedule, and we applied survival analysis using accelerated failure time models (AFT) to predict age of vaccine receipt based on timing of previous doses. RESULTS: 573,015 children were followed up until their fifth birthday, when they had 90.16 % coverage for two doses of measles, mumps, rubella (MMR) vaccine and 88.78% coverage for four doses of diphtheria, tetanus, pertussis (DTP) vaccine. Overall, the later the age at which a vaccine was due, the more delay in vaccination. Children of Black Ethnicity or from London showed deviating uptake patterns. If a child received their third DTP dose more than a year later than recommended, they would receive the next dose 2.7 times later than a child who was vaccinated on time. A smaller delay was found for children who did not receive first MMR dose on time. DISCUSSION: We showed that the risk of vaccination delay increased with the age of the child and significant delay of previous doses. Primary care data can help to promptly identify children at higher risk of delayed vaccination.

Potential Impacts of Mass Nutritional Supplementation on Measles Dynamics: A Simulation Study.

The bidirectional interaction between undernutrition and infection can be devastating to child health. Nutritional deficiencies impair immunity and increase susceptibility to infection. Simultaneously, infections compound undernutrition by increasing metabolic demand and impairing nutrient absorption. Treatment of acute malnutrition (wasting) can reverse some of its deleterious effects and reduce susceptibility to infectious diseases. Nutrition-specific approaches may be packaged with other interventions, including immunization, to support overall child health. To understand how mass nutritional supplementation, treatment of wasting, and vaccination affect the dynamics of a vaccine-preventable infection, we developed a population-level, compartmental model of measles transmission stratified by age and nutrition status. We simulated a range of scenarios to assess the potential reductions in measles infection and mortality associated with targeted therapeutic feeding for children who are wasted and with a mass supplementation intervention. Nutrition interventions were assumed to increase engagement with the health sector, leading to increased vaccination rates. We found that the combination of wasting treatment and mass supplementation coverage followed by an increase in vaccination coverage of non-wasted children from a baseline of 75% to 85%, leads to 34% to 57% and 65% to 77% reduction in measles infection and mortality and 56% to 60% reduction in overall mortality among wasted children, compared with the wasting treatment alone. Our work highlights the synergistic benefits that may be achieved by leveraging mass nutritional supplementation as a touch point with the health system to increase rates of vaccination and improve child survival beyond what would be expected from the additive benefits of each intervention.

Gaps in measles vaccination coverage in Kasese district, Western Uganda: results of a qualitative evaluation.

BACKGROUND: Despite the availability of a highly effective vaccine, measles remains a substantial public health problem in many countries including Uganda. In this study, conducted between June-August 2020 following a local outbreak, we sought to explore the factors that could affect measles vaccination coverage in rural western Uganda. METHODS: We conducted a descriptive study using qualitative data collection approaches in the Kasese district. The research team utilized purposive sampling to identify and select participants from the public health sector and district government. We conducted key informant interviews (KII) and one focus group discussion (FGD). Responses were recorded using portable electronic devices with the FGD and KII guide installed. Interviews were conducted at the health centre and district headquarters. Data was coded and analysed using ATLAS.ti version 8 software through deductive thematic analysis to identify key themes. RESULTS: Barriers to measles vaccination identified in this study were premised around six themes including: (i) availability of supplies and stock management, (ii) health worker attitudes and workload, (iii) financing of vaccination outreach activities, (iv) effectiveness of duty rosters (i.e., health workers' working schedules), (v) community beliefs, and (vi) accessibility of healthcare facilities. Respondents reported frequent vaccine supply disruptions, lack of resources to facilitate transportation of health workers to communities for outreach events, and health centre staffing that did not adequately support supplemental vaccination activities. Furthermore, community dependence on traditional medicine as a substitute for vaccines and long distances traveled by caregivers to reach a health facility were mentioned as barriers to vaccination uptake. CONCLUSIONS: Health system barriers limiting vaccination uptake were primarily logistical in nature and reflect inadequate resourcing of immunization efforts. At the same time, local beliefs favouring traditional medicine remain a persistent cultural barrier. These findings suggest an urgent need for more efficient supply management practices and resourcing of immunization outreaches in order to achieve the Uganda Ministry of Health's targets for childhood immunization and the prevention of disease outbreaks.

Interventions for High-Burden Infectious Diseases in Children and Adolescents: A Meta-analysis.

BACKGROUND: Approximately 2.2 million deaths were reported among school-age children and young people in 2019, and infectious diseases remain the leading causes of morbidity and mortality, especially in low and middle-income countries. We aim to synthesize evidence on interventions for high-burden infectious diseases among children and adolescents aged 5 to 19 years. METHODS: We conducted a comprehensive literature search until December 31, 2020. Two review authors independently screened studies for relevance, extracted data, and assessed risk of bias. RESULTS: We included a total of 31 studies, including 81 596 participants. Sixteen studies focused on diarrhea; 6 on tuberculosis; 2 on human immunodeficiency virus; 2 on measles; 1 study each on acute respiratory infections, malaria, and urinary tract infections; and 2 studies targeted multiple diseases. We did not find any study on other high burden infectious diseases among this age group. We could not perform meta-analysis for most outcomes because of variances in interventions and outcomes. Findings suggests that for diarrhea, water treatment, water filtration, and zinc supplementation have some protective effect. For tuberculosis, peer counseling, contingency contract, and training of health care workers led to improvements in tuberculosis detection and treatment completion. Continuation of cotrimoxazole therapy reduced the risk of tuberculosis and hospitalizations among human immunodeficiency virus-infected children and reduced measles complications and pneumonia cases among measles-infected children. Zinc supplementation led to a faster recovery in urinary tract infections with a positive effect in reducing symptoms. CONCLUSIONS: There is scarcity of data on the effectiveness of interventions for high-burden infectious diseases among school-aged children and adolescents.

Measles.

Measles is a highly contagious, potentially fatal, but vaccine-preventable disease caused by measles virus. Symptoms include fever, maculopapular rash, and at least one of cough, coryza, or conjunctivitis, although vaccinated individuals can have milder or even no symptoms. Laboratory diagnosis relies largely on the detection of specific IgM antibodies in serum, dried blood spots, or oral fluid, or the detection of viral RNA in throat or nasopharyngeal swabs, urine, or oral fluid. Complications can affect many organs and often include otitis media, laryngotracheobronchitis, pneumonia, stomatitis, and diarrhoea. Neurological complications are uncommon but serious, and can occur during or soon after the acute disease (eg, acute disseminated encephalomyelitis) or months or even years later (eg, measles inclusion body encephalitis and subacute sclerosing panencephalitis). Patient management mainly involves supportive therapy, such as vitamin A supplementation, monitoring for and treatment of secondary bacterial infections with antibiotics, and rehydration in the case of severe diarrhoea. There is no specific antiviral therapy for the treatment of measles, and disease control largely depends on prevention. However, despite the availability of a safe and effective vaccine, measles is still endemic in many countries and causes considerable morbidity and mortality, especially among children in resource-poor settings. The low case numbers reported in 2020, after a worldwide resurgence of measles between 2017 and 2019, have to be interpreted cautiously, owing to the effect of the COVID-19 pandemic on disease surveillance. Disrupted vaccination activities during the pandemic increase the potential for another resurgence of measles in the near future, and effective, timely catch-up vaccination campaigns, strong commitment and leadership, and sufficient resources will be required to mitigate this threat.

Small-molecule polymerase inhibitor protects non-human primates from measles and reduces shedding.

Measles virus (MeV) is a highly contagious pathogen that enters the human host via the respiratory route. Besides acute pathologies including fever, cough and the characteristic measles rash, the infection of lymphocytes leads to substantial immunosuppression that can exacerbate the outcome of infections with additional pathogens. Despite the availability of effective vaccine prophylaxis, measles outbreaks continue to occur worldwide. We demonstrate that prophylactic and post-exposure therapeutic treatment with an orally bioavailable small-molecule polymerase inhibitor, ERDRP-0519, prevents measles disease in squirrel monkeys (Saimiri sciureus). Treatment initiation at the onset of clinical signs reduced virus shedding, which may support outbreak control. Results show that this clinical candidate has the potential to alleviate clinical measles and augment measles virus eradication.

Linked vaccination coverage surveys plus serosurveys among Ethiopian toddlers undertaken three years apart to compare coverage and serologic evidence of protection in districts implementing the RED-QI approach.

In low and middle-income countries, estimating the proportion of vaccinated toddlers in a population is important for controlling vaccine-preventable diseases by identifying districts where immunization services need strengthening. Estimates measured before and several years after specific interventions can assess program performance. However, employing different methods to derive vaccination coverage estimates often yield differing results. METHODS: Linked vaccination coverage surveys and seroprotection surveys performed among ~300 toddlers 12-23 months of age in districts (woredas), one per region, of Ethiopia (total, ~900 toddlers) in 2013 to estimate the proportion vaccinated with tetanus toxoid (a proxy for pentavalent vaccine) and measles vaccine. The surveys were followed by implementation of the Reaching Every District using Quality Improvement (RED-QI) approach to strengthen the immunization system. Linked coverage/serosurveys were repeated in 2016 to assess effects of the interventions on vaccination coverage. Indicators included "documented coverage" (vaccination card and/or health facility register records) and "crude coverage" (documented plus parent/caretaker recall for children without cards). Seroprotection thresholds were IgG-ELISA tetanus antitoxin ≥0.05 IU/ml and plaque reduction neutralization (PRN) measles titers ≥120 mIU/ml. FINDINGS: Improved markers in 2016 over 2013 include coverage of pentavalent vaccination, vaccination timeliness, and fewer missed opportunities to vaccinate. In parallel, tetanus seroprotection increased in the 3 woredas from 59.6% to 79.1%, 72.9% to 83.7%, and 94.3 to 99.3%. In 2015, the Ethiopian government conducted supplemental measles mass vaccination campaigns in several regions including one that involved a project woreda and the campaign overlapped with the RED-QI intervention timeframe; protective measles PRN titers there rose from 31.0% to 50.0%. INTERPRETATION: The prevalence of seroprotective titers of tetanus antitoxin (stimulated by tetanus toxoid components within pentavalent vaccine) provides a reliable biomarker to identify children who received pentavalent vaccine. In the three study woredas, the RED-QI intervention appeared to improve immunization service delivery, as documented by enhanced pentavalent vaccine coverage, vaccination timeliness, and fewer missed vaccination opportunities. A measles mass vaccination campaign was followed by a markedly increased prevalence of measles PRN antibodies. Collectively, these observations suggest that wider implementation of RED-QI can strengthen immunization, and periodic linked vaccination surveys/serosurveys can monitor changes.

Psychometric properties of the adapted measles vaccine hesitancy scale in Sudan.

BACKGROUND: There is a need for reliable and validated tools to identify, classify, and quantify vaccine-hesitancy in low and middle-income countries, such as Sudan. We evaluated the psychometric properties of an adapted version of the measles vaccine hesitancy scale by assessing its reliability, convergent validity, and criterion validity in Sudan. The vaccine hesitancy scale (VHS) was originally developed by the WHO/SAGE Working Group of Vaccine Hesitancy. METHODS: A community-based survey among parents was conducted in February 2019 in Khartoum state. We conducted exploratory and confirmatory factor analysis to examine the structure of the adapted measles VHS (aMVHS). We computed Cronbach's alphas, correlations with other vaccine hesitancy measurements including the Parental Attitude towards Childhood Vaccination (PACV) and the Vaccine Confidence Index (VCI), and performed a Mann-Whitney U test for assessing the reliability and the convergent and criterion validity, respectively. Moreover, to examine whether the aMVHS can predict the child's vaccination status, the area under the curve (AUC) was estimated using receiver operator characteristic (ROC) curves. RESULTS: The questionnaire was completed by 500 parents. Most were women (87.2%) between the ages of 20 and 47 (M = 31.15, SD = 5.74). The factor analyses indicated that the aMVHS comprises of two factors (sub-scales): 'confidence' and 'complacency'. The aMVHS sub-scales correlated weakly to moderately with the PACV and VCI scales. The area under the curve was 0.499 at most (P >0.05) and the aMVHS score did hardly differ between actually vaccinated and non-vaccinated children. CONCLUSION: Our findings underscore that the aMVHS and its confidence and complacency sub-scales are reliable and have a moderately good convergent validity. However, the aMVHS has a limitation in predicting the concurrent child's vaccination status. More work is needed to revise and amend this aMVHS, particularly by additionally including the 'convenience' construct and by further evaluating its validity in other contexts.

Inequality in measles vaccination coverage in the "big six" countries of the WHO South-East Asia region.

The "big six" countries (Bangladesh, India, Indonesia, Myanmar, Nepal, and Thailand) in the World Health Organization South-East Asia Region (WHO SEAR) are currently facing severe challenges in measles elimination and consequent childhood mortality reduction, with inadequacies and inequalities in the coverage of the measles-containing-vaccine first-dose (MCV1) being major obstacles. However, these issues of inequality in MCV1 coverage have not yet been systematically examined. We used data from the latest Demographic and Health Surveys and Multiple Indicator Cluster Surveys. To provide a comprehensive picture of existing MCV1 coverage gaps, data were disaggregated by geographic location, as well as by socioeconomic and nutritional dimensions. National MCV1 coverage ranged from 77% in Myanmar to 92% in Thailand. Only nine of the 104 sub-national districts had achieved the 95% MCV1 coverage goal as set by the WHO. Geographic inequalities were more pronounced in countries with lower coverage levels. Areas in clusters with poor MCV1 coverage performances as well as disadvantaged socioeconomic profiles require increased attention. Inequalities were evident in all countries, except Thailand, and were more pronounced in the sectors of wealth, education, antenatal care (ANC) status, and vitamin A supplementation (VAS) when compared against the areas of gender and urban/rural residence. Wealth-related inequality in Bangladesh, education-related inequality in Indonesia, ANC-related inequalities in Myanmar and Nepal, and VAS-related inequalities in Indonesia and Myanmar were all noteworthy. Equity-oriented changes in policies focusing on health promotion and integrated interventions among disadvantaged populations need to be implemented in order to increase MCV1 coverage and reduce childhood mortality.

Progress Toward Measles Elimination - Eastern Mediterranean Region, 2013-2019.

In 1997, during the 41st session of the Regional Committee for the Eastern Mediterranean, the 21 countries in the World Health Organization (WHO) Eastern Mediterranean Region* (EMR) passed a resolution to eliminate† measles (1). In 2015, this goal was included as a priority in the Eastern Mediterranean Vaccine Action Plan 2016-2020 (EMVAP) (2), endorsed at the 62nd session of the Regional Committee (3). To achieve this goal, the WHO Regional Office for the Eastern Mediterranean developed a four-pronged strategy: 1) achieve ≥95% vaccination coverage with the first dose of measles-containing vaccine (MCV1) among children in every district of each country through routine immunization services; 2) achieve ≥95% vaccination coverage with a second MCV dose (MCV2) in every district of each country either through implementation of a routine 2-dose vaccination schedule or through supplementary immunization activities§ (SIAs); 3) conduct high-quality, case-based surveillance in all countries; and 4) provide optimal measles clinical case management, including dietary supplementation with vitamin A (4). This report describes progress toward measles elimination in EMR during 2013-2019 and updates a previous report (5). Estimated MCV1 coverage increased from 79% in 2013 to 82% in 2018. MCV2 coverage increased from 59% in 2013 to 74% in 2018. In addition, during 2013-2019, approximately 326.4 million children received MCV during SIAs. Reported confirmed measles incidence increased from 33.5 per 1 million persons in 2013 to 91.2 in 2018, with large outbreaks occurring in Pakistan, Somalia, and Yemen; incidence decreased to 23.3 in 2019. In 2019, the rate of discarded nonmeasles cases¶ was 5.4 per 100,000 population. To achieve measles elimination in the EMR, increased visibility of efforts to achieve the measles elimination goal is critically needed, as are sustained and predictable investments to increase MCV1 and MCV2 coverage, conduct high-quality SIAs, and reach populations at risk for not accessing immunization services or living in areas with civil strife.

Resurgence of Measles in Europe: A Systematic Review on Parental Attitudes and Beliefs of Measles Vaccine.

BACKGROUND AND OBJECTIVES: Europe has experienced a major resurgence of measles in recent years, despite the availability and free access to a safe, effective, and affordable vaccination measles, mumps and rubella vaccine (MMR). The main driver for this is suboptimal vaccine coverage. The three objectives of this study are to synthesize and critically assess parental attitudes and beliefs toward MMR uptake, to develop strategies and policy recommendations to effectively improve MMR vaccine uptake accordingly, and ultimately to identify areas for further research. METHODS: A systematic review was conducted using primary studies from PubMed, Medline, Embase, and Scopus published between 2011 and April 2019. Inclusion criteria comprised primary studies in English conducted in Europe and studying parental attitudes and behavior regarding MMR uptake. Data were extracted using an inductive grounded theory approach. RESULTS: In all, 20 high-quality studies were identified. Vaccine hesitancy or refusal were mainly due to concerns about vaccine safety, effectiveness, perception of measles risk and burden, mistrust in experts, and accessibility. Factors for MMR uptake included a sense of responsibility toward child and community health, peer judgement, trust in experts and vaccine, and measles severity. Anthroposophical and Gypsy, Roma, and Traveler populations presented unique barriers such as accessibility. CONCLUSION: A multi-interventional, evidence-based approach is vital to improve confidence, competence, and convenience of measles vaccination uptake. Healthcare professionals need an understanding of individual contextual attitudes and barriers to MMR uptake to tailor effective communication. Effective surveillance is needed to identify under-vaccinated populations for vaccination outreach programs to improve accessibility and uptake.

Progress Toward Measles Elimination - Pakistan, 2000-2018.

In 1997, the 21 countries in the World Health Organization (WHO) Eastern Mediterranean Region* (EMR) passed a resolution during the 41st session of the Regional Committee for the Eastern Mediterranean to eliminate measles† (1). In 2015, this goal was included as a priority in the Eastern Mediterranean Vaccine Action Plan 2016-2020 (2), approved at the 62nd session of the Regional Committee (3). To achieve measles elimination, the WHO Regional Office for the Eastern Mediterranean developed the following four-pronged strategy: 1) achieve ≥95% vaccination coverage with the first dose of measles-containing vaccine (MCV) among children in every district of each country through routine immunization services; 2) achieve ≥95% vaccination coverage with a second MCV dose in every district of each country either through implementation of a routine 2-dose vaccination schedule or through supplementary immunization activities (SIAs)§; 3) conduct high-quality, case-based measles surveillance in all countries; and 4) provide optimal measles clinical case management, including dietary supplementation with vitamin A (4). Pakistan, an EMR country with a population of approximately 200 million, accounts for nearly one third of the overall EMR population. This report describes progress and challenges toward measles elimination in Pakistan during 2000-2018. During the study period, estimated coverage with the first MCV dose (MCV1) increased from 57% in 2000 to 76% in 2017. The second MCV dose (MCV2) was introduced nationwide in 2009, and MCV2 coverage increased from 30% in 2009 to 45% in 2017. During 2000-2018, approximately 232.5 million children received doses of MCV during SIAs. Reported confirmed measles incidence increased from an average of 24.6 per 1 million persons during 2000-2009 to an average of 80.4 during 2010-2018, with peaks in 2013 (230.3) and 2018 (153.6). In 2017 and 2018, the rates of suspected cases discarded as nonmeasles after investigation were 2.1 and 1.5 per 100,000 population, reflecting underreporting of cases. To achieve measles elimination, additional efforts are needed to increase MCV1 and MCV2 coverage, develop strategies to identify and reach communities not accessing immunization services, and increase sensitivity of case-based measles surveillance in all districts.

Measles outbreaks in Italy: A paradigm of the re-emergence of vaccine-preventable diseases in developed countries.

Over the last decade, outbreaks of vaccine-preventable diseases have been reported in developed countries around the world. In particular, measles outbreaks have been ongoing in the European Union since 2017, with the majority of cases concentrated in Romania and Italy. Measles has been identified as a powerful indicator of the status of vaccination programs in a region, as outbreaks have been reported to quickly emerge as a result of underlying problems in the immunisation routine. This paper aims to report and critically comment on the factors underpinning the recent measles outbreaks in Italy, considering the psychological, cultural, social and political causes of vaccine hesitancy and refusal amongst the population. Data from government agencies including the Italian National Institute of Statistics (ISTAT) and the Italian National Institute of Health (ISS) are analysed to describe incidence and mortality trends from 1887 to the present day, including regional variations and the impact of measles vaccination coverage. The topic of compulsory vaccination is currently the object of heated debate in the Italian social and political panorama; this paper discusses the current state of the vaccination controversy in the Italian political discourse and its potential impact on immunisation policies and measles vaccine coverage amongst the population. A burgeoning body of evidence indicates that every effort should be made to bolster the existing legislation on mandatory vaccination through widespread health education campaigns aimed at improving scientific literacy amongst the Italian population with regards to the topic of immunisation.

Randomized Trial of 2 Versus 1 Dose of Measles Vaccine: Effect on Hospital Admission of Children After 9 Months of Age.

BACKGROUND: Two doses of measles vaccine (MV) might reduce the nonmeasles mortality rate more than 1 dose of MV does. The effect of 2 versus 1 dose on morbidity has not been examined. Within a randomized trial of the effect of 2 doses versus 1 dose of MV on mortality in Guinea-Bissau, we investigated the effect on hospital admissions. METHODS: Children were randomly assigned 1:2 to receive MV at 4.5 and 9 months of age or the currently recommended dose at 9 months. We compared hospital admission rates among children between 9 and 18 months of age in a Cox regression model with age as the underlying time scale. Half of the children had received neonatal vitamin A supplementation (NVAS) in another trial. The beneficial effect of MV at 4.5 and 9 months on mortality was limited to children who had not received NVAS; therefore, we investigated the interaction of MV with NVAS on admission rates. RESULTS: Among 5626 children (2 doses of MV, 1960 children; 1 dose of MV, 3666), we identified 311 hospital admissions of children between 9 and 18 months of age. Overall, compared to 1 dose of MV, 2 doses reduced the risk of hospital admission for children who had not received NVAS (hazard ratio [HR], 0.66 [95% confidence interval (CI), 0.47-0.93]), but we found no effect among NVAS recipients (HR, 1.16 [95% CI, 0.82-1.63]) (P = .02 for interaction). CONCLUSIONS: The benefit of 2 doses of MV was limited to children who had not received NVAS. NVAS is not generally recommended; hence, an early 2-dose measles vaccination policy might reduce hospital admissions more than the current policy of providing the first MV at 9 months of age. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00168558.

Measles outbreak investigation in Guji zone of Oromia Region, Ethiopia.

INTRODUCTION: Despite the increase of immunization coverage (administrative) of measles in the country, there are widespread outbreaks of measles. In this respect, we investigated one of the outbreaks that occurred in hard to reach kebeles of Guji Zone, Oromia region, to identify the contributing factors that lead to the protracted outbreak of measles. METHODS: We used a cross-sectional study design to investigate a measles outbreak in Guji zone, Oromia region. Data entry and analysis was performed using EPI-Info version 7.1.0.6 and MS-Microsoft Excel. RESULTS: In three months' time a total of 1059 suspected cases and two deaths were reported from 9 woredas affected by a measles outbreak in Guji zone. The cumulative attack rate of 81/100,000 population and case fatality ratio of 0.2% was recorded. Of these, 821 (77.5%) cases were < 15 years of age, and 742 (70%) were zero doses of measles vaccine. Although, all age groups were affected under five years old were more affected 495 (48%) than any other age groups. In response to the outbreak, an outbreak response immunization was organized at the 11th week of the epidemic, when the epidemic curve started to decline. 6 months to14 years old were targeted for outbreak response immunization and the overall coverage was 97 % (range: 90-103%). Case management with vitamin A supplementation, active case search, and health education was some of the activities carried out to curb the outbreak. CONCLUSION: We conclude that low routine immunization coverage in conjunction with low access to routine immunization in hard to reach areas, low community awareness in utilization of immunization service, inadequate cold chain management and delivery of a potent vaccine in hard to reach woredas/kebeles were likely contributed to the outbreak that's triggered a broad spread epidemic affecting mostly children without any vaccination. We also figured that the case-based surveillance lacks sensitivity and timely confirmation of the outbreak, which as a result outbreak response immunization were delayed. We recommend establishing reaching every child (REC) strategy in Guji zone with particular emphasis too hard reach areas to enhance the current immunization service, and furthermore to conduct data quality self-assessment or cluster coverage survey to verify the reported high vaccination coverage in some kebeles. We also recommend conducting the second opportunity as a form of supplemental immunization activities in 2-3 year interval or consider the national second dose introduction in the routine immunization system to improve population immunity. We further recommend that there is a need to boost the sensitivity of case-based surveillance system to be able to early detect, confirm and react to future epidemics.

The effect of early measles vaccination at 4.5 months of age on growth at 9 and 24 months of age in a randomized trial in Guinea-Bissau.

BACKGROUND: Providing an early, additional measles vaccine (MV) at 4.5 months of age has been shown to reduce child mortality in low-income countries. We studied the effects on growth at 9 and 24 months of age. METHODS: A randomized controlled trial was conducted in Guinea-Bissau from 2003-2007 including 6,648 children. Children were randomized 1:1:1 to receive Edmonston-Zagreb measles vaccine at 4.5 and 9 months of age (group A), no vaccine at 4.5 months and Edmonston-Zagreb measles vaccine at 9 months (group B), or no vaccine at 4.5 months and Schwarz measles vaccine at 9 months (group C) Data on anthropometrics were obtained at enrolment at 4.5 months of age and again at 9 and 24 months of age. Analyses were stratified by sex, season of enrolment, and neonatal vitamin A supplementation (NVAS) status, as all these factors have been shown to modify the effect of early MV on mortality. RESULTS: Overall there was no effect of early MV on anthropometry at 9 months. At 24 months children who had received early MV had a significantly larger mid-upper-arm-circumference (MUAC/in cm) (Difference = 0.08; 95% CI (0.02;0.14)) compared with children in the control group; this effect was most pronounced among girls (0.12 (0.03;0.20)). The effect of early MV on MUAC remained significant in the dry season and in girls who received placebo rather than NVAS. CONCLUSION: Early MV was associated with a larger MUAC particularly in girls. These results indicate that a two-dose measles vaccination schedule might not only reduce child mortality but also improve growth. TRIAL REGISTRATION: ClinicalTrials.gov NCT00168558 . Registered September 9, 2005, retrospectively registered.

Adding interventions to mass measles vaccinations in India.

OBJECTIVE: To quantify the impact on mortality of offering a hypothetical set of technically feasible, high-impact interventions for maternal and child survival during India's 2010-2013 measles supplementary immunization activity. METHODS: We developed Lives Saved Tool models for 12 Indian states participating in the supplementary immunization, based on state- and sex-specific data on mortality from India's Million Deaths Study and on health services coverage from Indian household surveys. Potential add-on interventions were identified through a literature review and expert consultations. We quantified the number of lives saved for a campaign offering measles vaccine alone versus a campaign offering measles vaccine with six add-on interventions (nutritional screening and complementary feeding for children, vitamin A and zinc supplementation for children, multiple micronutrient and calcium supplementation in pregnancy, and free distribution of insecticide-treated bednets). FINDINGS: The measles vaccination campaign saved an estimated 19 016 lives of children younger than 5 years. A hypothetical campaign including measles vaccine with add-on interventions was projected to save around 73 900 lives (range: 70 200-79 300), preventing 73 700 child deaths (range: 70 000-79 000) and 300 maternal deaths (range: 200-400). The most effective interventions in the whole package were insecticide-treated bednets, measles vaccine and preventive zinc supplementation. Girls accounted for 66% of expected lives saved (12 712/19 346) for the measles vaccine campaign, and 62% of lives saved (45 721/74 367) for the hypothetical campaign including add-on interventions. CONCLUSION: In India, a measles vaccination campaign including feasible, high-impact interventions could substantially increase the number of lives saved and mitigate gender-related inequities in child mortality.

Association of BCG, DTP, and measles containing vaccines with childhood mortality: systematic review.

OBJECTIVES:  To evaluate the effects on non-specific and all cause mortality, in children under 5, of Bacillus Calmette-Guérin (BCG), diphtheria-tetanus-pertussis (DTP), and standard titre measles containing vaccines (MCV); to examine internal validity of the studies; and to examine any modifying effects of sex, age, vaccine sequence, and co-administration of vitamin A. DESIGN:  Systematic review, including assessment of risk of bias, and meta-analyses of similar studies. STUDY ELIGIBILITY CRITERIA:  Clinical trials, cohort studies, and case-control studies of the effects on mortality of BCG, whole cell DTP, and standard titre MCV in children under 5. DATA SOURCES:  Searches of Medline, Embase, Global Index Medicus, and the WHO International Clinical Trials Registry Platform, supplemented by contact with experts in the field. To avoid overlap in children studied across the included articles, findings from non-overlapping birth cohorts were identified. RESULTS:  Results from 34 birth cohorts were identified. Most evidence was from observational studies, with some from short term clinical trials. Most studies reported on all cause (rather than non-specific) mortality. Receipt of BCG vaccine was associated with a reduction in all cause mortality: the average relative risks were 0.70 (95% confidence interval 0.49 to 1.01) from five clinical trials and 0.47 (0.32 to 0.69) from nine observational studies at high risk of bias. Receipt of DTP (almost always with oral polio vaccine) was associated with a possible increase in all cause mortality on average (relative risk 1.38, 0.92 to 2.08) from 10 studies at high risk of bias; this effect seemed stronger in girls than in boys. Receipt of standard titre MCV was associated with a reduction in all cause mortality (relative risks 0.74 (0.51 to 1.07) from four clinical trials and 0.51 (0.42 to 0.63) from 18 observational studies at high risk of bias); this effect seemed stronger in girls than in boys. Seven observational studies, assessed as being at high risk of bias, have compared sequences of vaccines; results of a subset of these suggest that administering DTP with or after MCV may be associated with higher mortality than administering it before MCV. CONCLUSIONS:  Evidence suggests that receipt of BCG and MCV reduce overall mortality by more than would be expected through their effects on the diseases they prevent, and receipt of DTP may be associated with an increase in all cause mortality. Although efforts should be made to ensure that all children are immunised on schedule with BCG, DTP, and MCV, randomised trials are needed to compare the effects of different sequences.