Waning of measles maternal antibody in infants in measles elimination settings – A systematic literature review

IntroductionMost infants are born with immunity to measles through maternal antibodies transferred in pregnancy, which decay over time. However, in measles elimination settings, where measles does not circulate endemically and most immunity is from immunization rather than infection, maternal antibody levels are lower. This results in infant immunity that wanes earlier, and a wider susceptibility gap between maternal antibody decay and infant immunization than in non-eliminated settings. We aimed to systematically quantify the extent and duration of protection from measles in infants in settings that have sustained measles elimination.MethodsWe conducted a systematic review of studies of measles maternal antibody waning in infants in measles elimination settings. We searched MEDLINE, Embase, CINAHL, Scopus, BIOSIS Previews, and Global Health databases for relevant studies. Studies were included if they were set in countries that had eliminated measles for ≥3 years, and if the study cohort included healthy, full-term, unvaccinated infants ≤12 months, born to healthy mothers, and reported a relevant measure of measles maternal antibody in infants. We assessed study quality using the MetaQAT tool.ResultsWe identified 4692 unique citations, eight of which met inclusion criteria. One study reported anti-measles antibody in cord blood, six reported antibody in infant sera, and one reported both. Two studies reported that 80 and 100% of infants were protected from measles at birth. One study reported no protection amongst 3–7 month old infants, and another reported limited protection in infants >4 months. The remaining studies reported the proportion of infants with detected antibody, but not the proportion immune.ConclusionAlthough limited, these data suggest that in settings that have sustained measles elimination, some infants are susceptible to measles well before the age of routine measles immunization. Setting-specific seroprevalence and vaccine effectiveness studies are required to evaluate this in different jurisdictions.     

Stop measles in Switzerland – The importance of travel medicine

BackgroundIn line with the worldwide strive to combat measles, the Swiss Federal Office of Public Heath (FOPH) launched a National Strategy for measles elimination 2011–2015. In this study, we highlight the importance of travel medicine consultations to complement measles vaccination programmes based on data from the Travel Clinic of the University of Zurich.MethodWe analysed measles vaccination data from the Zurich Travel Clinic between July 2010 and February 2016 and focused on three groups: (i) all clients who received the measles vaccination, (ii) all clients aged > two years who received the measles vaccination (“catch-up vaccination”), and (iii) all clients aged > two years and born after 1963 (“FOPH recommended catch-up vaccination”).Results107,669 consultations were performed from 2010 to 2016. In 12,470 (11.6%) of these, a measles vaccination was administered; 90.9% measles vaccinations were given during a pre-travel consultation, and 99.4% were administered to individuals aged > two years (“catch-up vaccinations”). An “FOPH recommended catch-up vaccination” was received by 13.6% of all Zurich Travel Clinic clients aged >2 years and born after 1963.ConclusionsIn this study, we highlight the importance of travel medicine consultations to enhance the measles vaccination coverage in the adult Swiss population.     

Seroepidemiology of measles in Catalonia (Spain) 1985–1986

A seroepidemiological study of measles immunological status was carried out among four different populations: schoolchildren of 6–7 years, 10–11 years and 13–14 years, and pregnant women of 18–45 years, in Catalonia, Spain; 1,213 children and 239 pregnant women were surveyed. The measurement of measles antibodies was made by indirect immunofluorescence, with antibody titres 1:8 considered as positive.The prevalence of measles antibodies was 82.9% in the 6–7 year old group, 87.2%, in the 10–11 year old group and 94.4% in the age group 13–14 years. Among pregnant women, the prevalence of antibodies was 96.2%.Two of the variables studied were associated with the prevalence of measles antibodies in schoolchildren: the disease antecedents and measles vaccination. In pregnant women aged 18–45 no variable had any stastically significant association with the prevalence of measles antibodies.     

The epidemiology of measles in Tianjin,China, 2005–2014

BackgroundMeasles incidence in China has declined over the last decade and elimination is targeted by 2020. Despite increases in routine immunization services and supplementary immunization activities (SIAs), periodic outbreaks continue to occur. In this paper, we examine measles epidemiology during 2005–2014 in Tianjin, China.MethodsMeasles case data were extracted from a web-based communicable disease surveillance system. We examined the socio-demographic characteristics of measles case patients, including age, sex, urbanicity, residency status, and vaccination history. Demographic characteristics of cases were compared with the general population.ResultsFrom January 1, 2005 to December 31, 2014, 12,466 measles cases in Tianjin were reported. Among the cases, 7179 (57.6%) were male and 5287 (42.4%) were female. Over time, more cases occurred in adults, and for the 2711 cases in 2014, the majority were either infants <1 year (558, 20.58%) or adults ≥20 years (2043, 75.36%). Municipal-wide SIAs in Tianjin occurred in 2008 and 2010 with reduction in measles cases the following year for both (189 cases in 2009, and 37 cases in 2011). The number of cases rebounded to pre-SIA levels or higher within 1–3 years following each SIA: 1990 cases in 2010 and 2711 cases in 2014. Vaccination status was reported as “none” or “unknown” for 84% of all reported measles cases.ConclusionsDespite the general decline in cases, measles outbreaks continue to occur. Although the SIAs reduce numbers in their immediate aftermath, case counts rebound 1–3 years after the intervention. Continued monitoring of cases through disease surveillance activities accompanied by targeted immunization activities, including to adults, can help ensure progress toward elimination.     

Epidemiology of a workplace measles outbreak dominated by modified measles cases at Kansai international airport,Japan, during august–september 2016

ObjectivesIn August 2016, a measles outbreak at Kansai International Airport was the first workplace measles outbreak since Japan was verified as having achieved measles-elimination status in March 2015. We investigated this outbreak with a focus on evaluating the ability of vaccinated individuals to transmit measles virus (MV).MethodsWe considered a case of laboratory-confirmed measles with onset between August 9 and September 29, 2016, among workers of Kansai International Airport. History of vaccination status with measles-containing vaccine (MCV) was confirmed by reviewing records. The potential sources of each MV infection were assessed by interviewing each infected worker about the clinical course of their infection and their behavioral history.ResultsOf 30 affected ground crews identified, 16 (53%) were vaccinated with ≥ 1 dose of MCV, 2 (7%) were unvaccinated, and 12 (40%) had an unknown vaccination status. The index case, a patient with classical measles with unknown vaccination status, presumably transmitted MV to all the subsequent 29 cases. The majority of patients (23, 77%; 15 vaccinated, 8 in unknown vaccination status) were diagnosed with modified measles due to mild illness. Modified measles were characterized clinically by signs of catarrh (4/23, 17%) in a few cases, with a median incubation period of 16 (range, 11–21) days. No onward transmission from vaccinated cases was suggested. An overseas traveler who visited the airport with measles symptoms was identified as the possible primary source of this outbreak.ConclusionsThe low MV transmission ability of vaccinated individuals was reaffirmed. Contact tracing of vaccinated modified measles cases can be limited to a person at high risk of infection (e.g., households, person with immunosuppression). To maintain measles-elimination status, completing two doses of MCV should be ensured, especially for international travelers and for those who are frequently exposed to these travelers, such as airport workers.     

Available studies fail to provide strong evidence of increased risk of diarrhea mortality due to measles in the period 4–26 weeks after measles rash onset

Background

Measles vaccination effectiveness studies showed dramatic decreases in all-cause mortality in excess of what would be expected from the prevention of measles disease alone. This invited speculation that measles infection may increase the risk of diarrhea morbidity and mortality subsequent to the acute phase of the disease. The aim of the present systematic review is to summarize the existing evidence in the publically available literature pertaining to the putative causal link between measles and diarrhea in the period 4–26 weeks following measles rash onset.

Methods

We searched the PubMed, Embase, Open Grey and Grey Literature Report databases for relevant literature using broad search terms. Prospective, retrospective and case-control studies in low- and middle-income countries involving children under five wherein relevant evidence were presented were included. Data were extracted from the articles and summarized.

Results

Fifty abstracts retrieved through the database searches met the initial screening criteria. Twelve additional documents were identified by review of the references of the documents found in the initial searches. Six documents representing five unique studies that presented evidence relevant to the research question were found. Four of the included studies took place in Bangladesh. One of the included studies took place in Sudan. Some measles vaccine effectiveness studies show lower diarrhea morbidity and mortality among the vaccinated. However, children who received vaccine may have differed in important ways from children who did not, such as health service utilization. Additionally, cohort studies following unvaccinated children showed no difference in diarrhea morbidity and mortality between cases and controls more than 4 weeks after measles rash onset. One study showed some evidence that severe measles may predispose children to gastroenteritis, but was not able to show a corresponding increase in the risk of diarrhea mortality.

Conclusions

The available evidence suggests that the risk of measles-associated diarrhea mortality is largely limited to the 5-week period 1 week prior to and 4 weeks after measles rash onset, and that there is no increased risk of diarrhea mortality in the longer-term caused by measles.

     

Evaluation of measles–rubella vaccination for mothers in early puerperal phase

BackgroundThe postpartum period is an ideal opportunity to vaccinate mothers with inadequate immunity to vaccine-preventable diseases including measles and rubella.MethodsA prospective study of measles–rubella (MR) vaccination in the early puerperal phase was conducted in 171 mothers, who had insufficient antibody titers when screened for immunity to measles (≤1:4 on the neutralization test [NT]) or rubella (≤1:16 on the hemagglutination inhibition [HI] test) during pregnancy. To evaluate the efficacy of MR vaccination in the postpartum period, we determined their post-vaccination antibody titers and immune responses to vaccination, and investigated the association between these and their prolactin (PRL) levels and Th1/Th2 ratios at the time of vaccination. We also examined the passage of viral RNA and antigen into breast milk.ResultsOf the 169 participants who completed the study schedule, 117 and 101 had low antibody titers against measles and rubella, respectively. In the measles-seronegative group, the antibody-positive rate was 87% on the NT assay, and the NT geometric mean antibody titer was 11.4 (95% confidence interval [CI], 10.0–13.0). In the rubella-seronegative group, the antibody-positive rate was 88% on the HI test assay, and the HI geometric mean antibody titer was 64.0 (95% CI, 53.9–76.0). There was no association between the post-vaccination antibody titers and the PRL levels or Th1/Th2 ratios at the time of vaccination. In the rubella-seronegative group, subjects with higher Th1/Th2 ratios showed higher rates of responsiveness than those with lower ratios (P = 0.045). Although measles virus RNA was isolated from the breast milk of two vaccinated mothers, breastfeeding was not associated with clinical disease in any infants.ConclusionMR vaccination in the early puerperal phase is considered an effective way to prevent the diseases, regardless of the mother's immunological status and hormonal milieu.     

Description of a large measles epidemic in Democratic Republic of Congo, 2010–2013

Background

Although measles mortality has declined dramatically in Sub-Saharan Africa, measles remains a major public health problem in countries like the Democratic Republic of Congo (DRC). Here, we describe the large measles epidemic that occurred in the Democratic Republic of Congo between 2010 and 2013 using data from the national surveillance system as well as vaccine coverage surveys to provide a snapshot of the epidemiology of measles in DRC.

Methods

Standardized national surveillance data were used to describe measles cases from 2010 to 2013. Attack rates and case fatality ratios were calculated and the temporal and spatial evolution of the epidemic described. Data on laboratory confirmation and vaccination coverage surveys as a part of routine program monitoring are also presented.

Findings

Between week 1 of 2010 and week 45 of 2013, a total of 294,455 cases and 5,045 deaths were reported. The cumulative attack rate (AR) was 0.4%. The Case Fatality Ratio (CFR) was 1.7% among cases reported in health structures through national surveillance. A total of 186,178 cases (63%) were under 5 years old, representing an estimated AR of 1.4% in this age group. Following the first mass vaccination campaigns, weekly reported cases decreased by 21.5%. Results of post-vaccination campaign coverage surveys indicated sub-optimal (under 95%) vaccination coverage among children surveyed.

Conclusions

The data reported here highlight the need to seek additional means to reinforce routine immunization as well as ensure the timely implementation of Supplementary Immunization Activities to prevent large and repeated measles epidemics in DRC. Although reactive campaigns were conducted in response to the epidemic, strategies to ensure that children are vaccinated in the routine system remains the foundation of measles control.

     

Can measles be eradicated globally?

Measles is one of the most infectious diseases. Before measles vaccine was introduced, nearly everyone contracted the disease at some point in childhood. By the late 1980s, most countries had incorporated measles vaccine into their routine immunization programmes. Globally, about 800 000 children nevertheless still die from measles annually, half of them in Africa. Eradicating measles would therefore play an important role in improving children's survival. The 24th Pan American Sanitary Conference in 1994 established a goal of eradicating measles from the Americas. Progress to date has been remarkable and the disease is no longer endemic in the Americas, with most countries having documented interruption of transmission. As of November 2003, 12 months had elapsed since the last indigenous case was detected in Venezuela. This experience shows that measles transmission can be interrupted, and that this can be sustained over a long period of time. Global eradication is feasible if an appropriate strategy is implemented. Even under a new paradigm in which immunization is not discontinued after measles is eradicated, eradication will be a good investment to avoid expensive epidemics and save the lives of almost one million children annually. A world free of measles by 2015 is not a dream.     

Declining measles antibodies in the era of elimination: Australia’s experience

BackgroundAustralia is one of only a few countries with a long-standing and consistent serosurveillance program. We conducted a national serosurvey in 2012–2013 to estimate population seroprevalence of measles-specific IgG and the effective reproduction number, R, and compare the results with the three previous serosurveys (1996–1999, 2002 and 2007) to examine trends following a decade of sustained measles control.Methods2729 residual sera from 1 to 49 year olds were tested using the Enzygnost anti-measles IgG enzyme immunoassay (EIA). All sera in the equivocal range by EIA on re-testing and a random sample of low positive and negative sera were later tested by a microneutralisation assay. R was calculated from weighted estimates of the proportion seronegative by age using a previously developed contact matrix.ResultsIn the 2012–13 serosurvey, anti-measles IgG seropositivity for 1–49 year olds was 80.8% (95% CI: 79.4–82.3%) and 8.9% (95% CI: 7.8–10.0%) had equivocal antibody levels. The increasing proportion of seronegative and equivocal individuals in age groups 10–39 years continued a trend seen in previous serosurveys. There was also an increase in equivocal results among 2–4 and 5–9 year old children, >90% of whom were recently vaccinated. R increased from 0.57 in 1999 to above the epidemic threshold of 1 in 2012–13 (R = 1.7). All 20 EIA negative sera, 238/241 (98.8%) equivocal sera, and 89/92 (96.7%) low positive sera had a titre <10 (negative) in the measles microneutralisation assay.ConclusionsA number of countries with sustained measles control have now demonstrated that measles-specific IgG antibodies decline with time since vaccination. As there is good epidemiologic evidence of population-level protection, the implications of declining measles-specific IgG antibody levels for maintaining measles elimination are unclear. Novel studies to determine correlates of protection against measles transmission and disease in the post-elimination era are needed to help answer this question.     

Following in the footsteps of smallpox: can we achieve the global eradication of measles?

Background  

Although an effective measles vaccine has been available for almost 40 years, in 2000 there were about 30 million measles infections worldwide and 777,000 measles-related deaths. The history of smallpox suggests that achieving measles eradication depends on several factors; the biological characteristics of the organism; vaccine technology; surveillance and laboratory identification; effective delivery of vaccination programmes and international commitment to eradication.     

Measles in the United Kingdom 1990–2008 and the effectiveness of measles vaccines

We identified all children in the UK General Practice Research Database diagnosed with measles from 1990 to 2008 and calculated annual incidence according to age and geographic region by dividing the number of cases per year by the number of children who were active in the population. We evaluated the effectiveness of the measles vaccines by comparing the vaccination histories of children who were diagnosed with measles (cases) to children who were not (controls). The annual incidence of measles fell after the introduction of the MMR vaccine in late 1988. However, a modest outbreak of measles occurred in 1994, leading to large nationwide programs to immunize children. Since 1996, the incidence of measles has fallen by more than 80%. Prior measles vaccination is highly effective and has substantially reduced the risk of measles.     

The progress of the Polio Eradication Initiative: what prospects for eradicating measles?

Although various attempts have been made to eradicate infectious diseases, only smallpox has been eradicated to date. Polio is targeted for eradication in 2000 and already planning has begun for the eradication of measles. However, before we commit to a measles eradication effort, we must examine the lessons to be learned from polio eradication. Of particular importance is the debate over whether resources should be invested in 'horizontal' or 'vertical' programmes. The outcome of these debates will have a very deep and lasting impact on global health development in years to come. Collaboration between targeted programmes and the primary health care sector through polio and measles eradication efforts will help bring about the necessary balance between goal-oriented programmes, which are subject to quality control and can be evaluated by measurable outcomes, and broader efforts to build up sustainable health infrastructure.     

Genetic Aspects of Scurvy and the European Famine of 1845–1848

The view of scurvy being exclusively a nutritional disorder needs to be updated. Genetic polymorphisms of HFE and haptoglobin (Hp) may explain the geographic variability of mortality caused by the European famine of the mid-19th century. In this period, potatoes had fallen victim to the potato blight and Ireland was more severely hit than continental Europe. Hereditary hemochromatosis is a genetic disorder with mutations in the HFE gene, characterized by iron overload (with a reduced vitamin C stability) and with a predominance of affected men. The Irish have the world’s highest frequency of the C282Y mutation and the particular iron metabolism of the Irish helps to understand the size of the catastrophe and the observed overrepresentation of male skeletons showing scurvy. Hp is a plasma α₂-glycoprotein characterized by 3 common phenotypes (Hp 1-1, Hp 2-1 and Hp 2-2). When the antioxidant capacity of Hp is insufficient, its role is taken over by hemopexin and vitamin C. The relative number of scurvy victims corresponds with the Hp 2-2 frequency, which is associated with iron conservation and has an impact on vitamin C stability. As iron is more abundant in males, males are overrepresented in the group of skeletons showing scurvy signs.     

Predictors of measles vaccination coverage among children 6–59 months of age in the Democratic Republic of the Congo

BackgroundMeasles is a significant contributor to child mortality in the Democratic Republic of the Congo (DRC), despite routine immunization programs and supplementary immunization activities (SIA). Further, national immunization coverage levels may hide disparities among certain groups of children, making effective measles control even more challenging. This study describes measles vaccination coverage and reporting methods and identifies predictors of vaccination among children participating in the 2013–2014 DRC Demographic and Health Survey (DHS).MethodsWe examined vaccination coverage of 6947 children aged 6–59 months. A multivariate logistic regression model was used to identify predictors of vaccination among children reporting vaccination via dated card in order to identify least reached children. We also assessed spatial distribution of vaccination report type by rural versus urban residence.ResultsUrban children with educated mothers were more likely to be vaccinated (OR = 4.1, 95% CI: 1.6, 10.7) versus children of mothers with no education, as were children in wealthier rural families (OR = 2.9, 95% CI: 1.9, 4.4). At the provincial level, urban areas more frequently reported vaccination via dated card than rural areas.ConclusionsResults indicate that, while the overall coverage level of 70% is too low, socioeconomic and geographic disparities also exist which could make some children even less likely to be vaccinated. Dated records of measles vaccination must be increased, and groups of children with the greatest need should be targeted. As access to routine vaccination services is limited in DRC, identifying and targeting under-reached children should be a strategic means of increasing country-wide effective measles control.     

Prevalence of measles susceptibility among health care workers in a UK hospital. Does the UK need to introduce a measles policy for its health care workers?

OBJECTIVES: First, to determine the prevalence of measles non-immunity in a group of health care workers (HCW), and secondly, to investigate what pre-employment screening for measles is carried out by NHS occupational health departments. METHODS: Two hundred and eighteen HCWs with patient contact on the medical wards at Addenbrooke's hospital provided an oral fluid sample and answered a questionnaire. A postal survey of Association of National Health Occupational Physicians Society (ANHOPS) members was conducted to assess whether UK NHS Trusts identify measles non-immune individuals. RESULTS: Of the HCWs tested, 3.3% of were found to be non-immune to measles (both oral fluid and confirmatory serum sample were measles IgG negative). Less than one third of a sample of 80 NHS occupational health departments enquired about measles immunity. CONCLUSION: The prevalence of measles non-immune health care workers is low, but with a fall in uptake of MMR immunization and increased likelihood of measles outbreaks, it is important to identify these at-risk individuals. Serum testing is the most reliable method to use. Oral fluid testing and history of measles disease or vaccination are unreliable methods of identifying non-immune individuals. To achieve complete immunity, it is cost-effective to screen and then offer immunization. NHS trusts vary greatly in their measles policies for health care workers.