The Lancet Infectious Diseases
May 2016 Volume 16 Number 5 p507-618 e64-e81
http://www.thelancet.com/journals/laninf/issue/current
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Editorial
Ebola PHEIC is over but emergency continues
The Lancet Infectious Diseases
Summary
On March 29, WHO Director-General Margaret Chan announced that the outbreak of Ebola virus disease in countries of west Africa was no longer a Public Health Emergency of International Concern (PHEIC). This decision was taken because, in the opinion of the International Health Regulations Emergency Committee on Ebola, the outbreak is no longer an extraordinary event, there is little risk of international spread, and affected countries have the capacity to rapidly respond to new cases. The Emergency Committee acknowledged that new clusters will continue to occur, but that they are happening at a decreasing frequency.
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Comment
Managing the risks of vaccine hesitancy and refusals
Ève Dubé, Noni E MacDonald
Published Online: 04 February 2016
DOI: http://dx.doi.org/10.1016/S1473-3099(16)00028-1
Summary
In The Lancet Infectious Diseases, John Glasser and colleagues1 report the results of a spatially-stratified model to better understand the dynamics of disease outbreaks and the link with vaccine hesitancy and refusal. Using data for 39 132 children starting elementary school in San Diego County, CA, USA, in 2008 (2% of whom had a personal-belief exception to vaccines), the authors show the effect of heterogeneity on the reproduction numbers for measles, mumps, and rubella. Although the mean population immunities for measles, mumps, and rubella were similar to the population-immunity thresholds, modelling for non-random mixing (unvaccinated children tend to preferentially mix with other unvaccinated children) and heterogeneity caused the basic reproductive numbers to increase by 70%, meaning that an introduced infectious person could cause an outbreak.
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Articles
Group B streptococcus vaccination in pregnant women with or without HIV in Africa: a non-randomised phase 2, open-label, multicentre trial
Robert S Heyderman, Shabir A Madhi, Neil French, Clare Cutland, Bagrey Ngwira, Doris Kayambo, Robert Mboizi, Anthonet Koen, Lisa Jose, Morounfolu Olugbosi, Frederik Wittke, Karen Slobod, Peter M Dull
Open Access
Summary
Background
Neonates born to women infected with HIV are at increased risk for invasive group B streptococcus (GBS) disease. We aimed to compare safety and immunogenicity of trivalent glycoconjugate GBS vaccine in pregnant women with and without HIV in Malawi and South Africa.
Methods
In our non-randomised phase 2, open-label, multicentre study, we recruited pregnant women attending two antenatal clinics, one in Blantyre, Malawi, and one in Soweto, Johannesburg, South Africa. Participants were divided into three groups on the basis of their HIV infection status (no infection, infection and high CD4 cell count [>350 cells per μL], and infection and low CD4 cell count [>50 to ≤350 cells per μL]) and received a 5 μg dose of glycoconjugate GBS vaccine (serotypes Ia, Ib, and III, with CRM197 [Novartis Vaccines, Siena, Italy]) intramuscularly at 24–35 weeks’ gestation. GBS serotype-specific antibody concentrations were measured before vaccination (day 1), day 15, day 31, and at delivery, and in infants at birth and day 42 of life. The primary outcomes were safety in mothers and infants and the amount of placental transfer of GBS serotype-specific antibodies from mothers to their infants. All immunogenicity and safety analyses were done on the full analysis set, including participants who, or whose mother, correctly received the vaccine and who provided at least one valid assessable serum sample. This study is registered with ClinicalTrials.gov, number NCT01412801.
Findings
270 women and 266 infants were enrolled between Sept 26, 2011, and Dec 4, 2012 (90 women and 87 infants without HIV, 89 and 88 with HIV and high CD4 cell counts, and 91 and 91 with HIV and low CD4 cell counts, respectively). Seven women were lost to follow-up, six withdrew consent, one died, and two relocated. Eight infants died or were stillborn and two were lost to follow-up. Across serotypes, fold change in antibody concentrations were higher for the HIV-uninfected group than the HIV-infected groups. Transfer ratios were similar across all three groups (0·49–0·72; transfer ratio is infant geometric mean antibody concentration in blood collected within 72 h of birth divided by maternal geometric mean antibody concentration in blood collected at delivery); however, at birth, maternally derived serotype-specific antibody concentrations were lower for infants born to women infected with HIV (0·52–1·62 μg/mL) than for those born to women not infected with HIV (2·67–3·91 μg/mL). 151 (57%) of 265 women reported at least one solicited adverse reaction: 39 (45%) of 87 women with HIV and low CD4 cell counts, 52 (59%) of 88 women with HIV and high CD4 cell counts, and 60 (67%) of 90 women in the HIV-uninfected group. 49 (18%) of 269 women had at least one adverse event deemed possibly related to the vaccine (six [7%] in the HIV and low CD4 cell count group, 12 [13%] in the HIV and high CD4 cell count group, and 21 [23%] in the HIV-uninfected group), as did three (1%) of 266 neonates (zero, two [1%], and one [1%]); none of these events was regarded as serious.
Interpretation
The vaccine was less immunogenic in women infected with HIV than it was in those not infected, irrespective of CD4 cell count, resulting in lower levels of serotype-specific maternal antibody transferred to infants, which could reduce vaccine protection against invasive GBS disease. A validated assay and correlate of protection is needed to understand the potential protective value of this vaccine.
Funding
Novartis Vaccines and Diagnostics division (now part of the GlaxoSmithKline group of companies), Wellcome Trust UK, Medical Research Council: Respiratory and Meningeal Pathogens Research Unit
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Articles
Effect of vaccination programmes on mortality burden among children and young adults in the Netherlands during the 20th century: a historical analysis
Maarten van Wijhe, Scott A McDonald, Hester E de Melker, Maarten J Postma, Jacco Wallinga
Summary
Background
In the 20th century, childhood mortality decreased rapidly, and vaccination programmes are frequently suggested as a contributing factor. However, quantification of this contribution is subject to debate or absent. We present historical data from the Netherlands that allow us to quantify the reduction in childhood mortality burden for vaccine-preventable diseases in this period as a function of vaccination coverage.
Methods
We retrieved cause-specific and age-specific historical mortality data from Statistics Netherlands from 1903 to 2012 (for Dutch birth cohorts born from 1903 to 1992), and data for vaccination coverage since the start of vaccination programmes from the Dutch Health Care Inspectorate and the Dutch National Institute for Public Health and the Environment. We also obtained birth and migration data from Statistics Netherlands. We used a restricted mean life-time method to estimate cause-specific mortality burden among children and young adults for each birth cohort as the years of life lost up to age 20 years, excluding migration as a variable because this did not affect the results. To correct for long-term trends, we calculated the cause-specific contribution to the total childhood mortality burden.
Findings
In the prevaccination era, the contribution to mortality burden was fairly constant for diphtheria (1·4%), pertussis (3·8%), and tetanus (0·1%). Around the start of mass vaccinations, these contributions to the mortality burden decreased rapidly to near zero. We noted similar patterns for poliomyelitis, mumps, and rubella. The number of deaths due to measles around the start of vaccination in the Netherlands were too few to detect an accelerated rate of decrease after mass vaccinations were started. We estimate that mass vaccination programmes averted 148 000 years of life lost up to age 20 years (95% prediction interval 110 000–201 000) among children born before 1992. This corresponds to about 9000 deaths averted (6000–12 000).
Interpretation
Our historical time series analysis of mortality and vaccination coverage shows a strong association between increasing vaccination coverage and diminishing contribution of vaccine-preventable diseases to overall mortality. This analysis provides further evidence that mass vaccination programmes contributed to lowering childhood mortality burden.
Funding
Dutch Ministry of Health, Welfare and Sport.
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Articles
The effect of heterogeneity in uptake of the measles, mumps, and rubella vaccine on the potential for outbreaks of measles: a modelling study
John W Glasser, Zhilan Feng, Saad B Omer, Philip J Smith, Lance E Rodewald
Summary
Background
Vaccination programmes to prevent outbreaks after introductions of infectious people aim to maintain the average number of secondary infections per infectious person at one or less. We aimed to assess heterogeneity in vaccine uptake and other characteristics that, together with non-random mixing, could increase this number and to evaluate strategies that could mitigate their impact.
Methods
Because most US children attend elementary school in their own neighbourhoods, surveys of children entering elementary school (age 5 years before Sept 1) allow assessment of spatial heterogeneity in the proportion of children immune to vaccine-preventable diseases. We used data from a 2008 school-entry survey by the Immunization Division of the California Department of Public Health to obtain school addresses; numbers of students enrolled; proportions of enrolled students who had received one or two doses of the measles, mumps, and rubella (MMR) vaccine; and proportions with medical or personal-belief exemptions. Using a mixing model suitable for spatially-stratified populations, we projected the expected numbers of secondary infections per infectious person for measles, mumps, and rubella. We also mapped contributions to this number for measles in San Diego County’s 638 elementary schools and its largest district, comprising 200 schools (31%). We then modelled the effect on measles’ realised reproduction number (RV) of the following plausible interventions: vaccinating all children with personal-belief exemptions, increasing uptake by 10% to 50% in all low-immunity schools (<90% of students immune) or in only influential (effective daily contact rates >3 or contacts inter-school >30%) low-immunity schools, and increasing private school uptake to the public school average.
Findings
In 2008, 39 132 children began elementary school in San Diego County, CA, USA. At entry to school, 97% had received at least one dose of the MMR vaccine, with 2·5% having personal-belief exemptions. We note substantial heterogeneity in immunity throughout the county. Although the average population immunities for measles, mumps, and rubella (92%, 87%, 92%) were similar to the population-immunity thresholds in homogeneous, randomly-mixing populations (91%, 88%, 76%), after accounting for heterogeneity and non-random mixing, the basic reproduction numbers increased by 70%, meaning that introduced pathogens could cause outbreaks. The impact of our modelled interventions ranged from negligible to a nearly complete reduction in the outbreak potential of measles. The most effective intervention to lower the realised reproduction number (RV 3·39) was raising immunity by 50% in 114 schools with low immunity (RV 1·02), but raising immunity by this level in only influential, low-immunity schools also was effective (RV 2·02). The effectiveness of vaccinating the 972 children with personal-belief exemptions was similar to that of targeting all low-immunity schools (RV 1·11). Targeting only private schools had little effect.
Interpretation
Our findings suggest that increasing vaccine uptake could prevent outbreaks such as that of measles in San Diego in 2008. Vaccinating children with personal-belief exemptions was one of the most effective interventions that we modelled, but further research on mixing in heterogeneous populations is needed.
Funding
None.