Extreme mortality during a historical measles outbreak on Rotuma is consistent with measles immunosuppression.

Until the early twentieth century, populations on many Pacific Islands had never experienced measles. As travel to the Pacific Islands by Europeans became more common, the arrival of measles and other pathogens had devastating consequences. In 1911, Rotuma in Fiji was hit by a measles epidemic, which killed 13% of the island population. Detailed records show two mortality peaks, with individuals reported as dying solely from measles in the first and from measles and diarrhoea in the second. Measles is known to disrupt immune system function. Here, we investigate whether the pattern of mortality on Rotuma in 1911 was a consequence of the immunosuppressive effects of measles. We use a compartmental model to simulate measles infection and immunosuppression. Whilst immunosuppressed, we assume that individuals are vulnerable to dysfunctional reactions triggered by either (i) a newly introduced infectious agent arriving at the same time as measles or (ii) microbes already present in the population in a pre-existing equilibrium state. We show that both forms of the immunosuppression model provide a plausible fit to the data and that the inclusion of immunosuppression in the model leads to more realistic estimates of measles epidemiological parameters than when immunosuppression is not included.

Factors associated with return of home oral fluid kits by suspected cases of measles, cohort study, London and South East of England, 2016-2018.

A testing rate for measles above 80% is required by the WHO European Region Measles Elimination strategy to verify elimination. To comply with this rate, we explored factors associated with the return of oral fluid kits (OFK) by suspected measles cases. We described the cases and conducted a mixed-effects analysis to assess the relationship between socio-demographic and public health management characteristics and the likelihood of returning an OFK to the reference laboratory. Of 3,929 cases who were sent a postal OFK, 2,513 (67%) returned the kit. Adjusting for confounding, registration with a general practitioner (GP) (aOR:1.48, 95%CI:1.23-1.76) and living in a less deprived area (aOR:1.35, 95%CI:1.04-1.74) were associated with an increased likelihood of returning the OFK. The odds of returning the OFK also increased if the HPT contacted the parents/guardians of all cases prior to sending the kit and confirmed their address (aOR:2.01, 95%CI:1.17-3.42). Cases notified by a hospital (aOR:1.94, 95%CI:1.31-2.87) or GP (aOR:1.52; 95%CI:1.06-2.16) also had higher odds of returning the OFK. HPTs may want to consider these factors when managing suspected cases of measles since this may help in increasing the testing rates to the WHO-recommended level.

Determinants of measles persistence in Beijing, China: A modelling study.

In Beijing, the capital of China, routine measles mass vaccination has been in place for decades with high coverage; and since the 2000s, catch-up vaccination programmes have been implemented for migrant workers coming to the city. However, measles epidemics in Beijing persisted. Here, we explored the contributing factors of persistent measles transmission in Beijing using an epidemic model in conjunction with a particle filter. Model inputs included data on birth, death, migration, and vaccination. We formulated a series of hypotheses covering the impact of migrant influx, early waning of maternal immunity, and increased mixing among infants; we compared the plausibility of the hypotheses based on model fit to age-grouped, weekly measles incidence data from January 2005 to December 2014, and out-of-fit prediction during 2015-2019. Our best models showed close agreement with the data, and the out-of-fit prediction generally captured the trend of measles incidence from 2015 to 2019. We found that large influx of migrants with considerably higher susceptibility likely contributed to the persistent measles transmission in Beijing. Our findings suggest that stronger catch-up vaccination programmes for migrants may help eliminate measles transmission in Beijing.

Evaluation of a rapid diagnostic test for measles IgM detection; accuracy and the reliability of visual reading using sera from the measles surveillance programme in Brazil, 2015.

Laboratory-based case confirmation is an integral part of measles surveillance programmes; however, logistical constraints can delay response. Use of RDTs during initial patient contact could enhance surveillance by real-time case confirmation and accelerating public health response. Here, we evaluate performance of a novel measles IgM RDT and assess accuracy of visual interpretation using a representative collection of 125 sera from the Brazilian measles surveillance programme. RDT results were interpreted visually by a panel of six independent observers, the consensus of three observers and by relative reflectance measurements using an ESEQuant Reader. Compared to the Siemens anti-measles IgM EIA, sensitivity and specificity of the RDT were 94.9% (74/78, 87.4-98.6%) and 95.7% (45/47, 85.5-99.5%) for consensus visual results, and 93.6% (73/78, 85.7-97.9%) and 95.7% (45/47, 85.5-99.5%), for ESEQuant measurement, respectively. Observer agreement, determined by comparison between individuals and visual consensus results, and between individuals and ESEQuant measurements, achieved average kappa scores of 0.97 and 0.93 respectively. The RDT has the sensitivity and specificity required of a field-based test for measles diagnosis, and high kappa scores indicate this can be accomplished accurately by visual interpretation alone. Detailed studies are needed to establish its role within the global measles control programme.

High number of hospitalisations and non-classical presentations: lessons learned from a measles outbreak in 2017, Belgium.

We describe and analyse an outbreak of measles that affected Belgium early 2017. In total, 289 cases were reported, mostly (53%) in people 15 years or older. For 133 (46%) vaccination status was unknown and a further 117 (41%) were not vaccinated. According to national guidelines, 83 of the unvaccinated cases (29% of total cases) should have received minimum one dose of vaccine, but did not. One in five cases (21%) did not present with the classical triad of fever, rash and any of coryza, conjunctivitis or cough. Rash was the most sensitive symptom, being absent in only six cases. A large proportion of cases (125/289, 43%) required hospitalisation. In hospitalised patients, the most commonly observed complications were hepatic disorders (present in 58/125 hospitalised patients, 46%). Thirty-six of the cases (12%) were in healthcare workers and nosocomial spread contributed importantly to the outbreak. Older age at presentation, altered clinical presentations and presence of complications like hepatitis can delay the correct diagnosis of measles. Clinicians should maintain a high index of suspicion in any individual presenting with rash. If the elimination target is to be reached, catch-up vaccination campaigns should be intensified and target young adults and health care workers.

Measles and rubella seroprevalence in a population of young adult blood donors, France 2013.

As part of the evaluation of the French plan for the elimination of measles and rubella, we conducted a seroprevalence survey in 2013, aimed at updating seroprevalence data for people 18-32 years old. A secondary objective was to estimate measles incidence in this population during the 2009-2011 outbreak, and thus estimate the exhaustiveness of measles mandatory reporting. We used a cross-sectional survey design, targeting blood donors 18-32 years old, living in France since 2009, who came to give blood in a blood collecting site. We included 4647 people in metropolitan France, 806 people in Réunion Island and 496 in the French Caribbean. A further 3942 individuals were interviewed in the south-east region of metropolitan France to estimate the exhaustiveness of measles mandatory reporting. One of the main findings of this survey is that the proportion of people 18-32 years old susceptible to both measles and rubella infections remained high in France in 2013, 9.2% and 5.4%, respectively, in metropolitan France, even after the promotion campaigns about vaccination catch-up during and following the major measles epidemic in 2009-2011. Applying our results to French census data would suggest that around 1 million people aged 18-32 years old are currently susceptible to measles in France, despite this age group being one of the vaccination targets of the national measles elimination plan. Another important finding is that only an estimated 45% of the true number of cases in this age group was actually notified, despite notification being mandatory.

Genetic characterisation of Measles virus variants identified during a large epidemic in Milan, Italy, March-December 2017.

In 2017, Italy experienced a large measles epidemic with 5408 cases and four deaths. As Subnational Reference Laboratory of the Measles and Rubella surveillance NETwork (MoRoNET), the EpiSoMI (Epidemiology and Molecular Surveillance of Infections) Laboratory (University of Milan) set up rapid and active surveillance for the complete characterisation of the Measles virus (Mv) responsible for the large measles outbreak in Milan and surrounding areas (Lombardy, Northern Italy). The aims of this study were to describe the genetic profile of circulating viruses and to track the pathway of measles transmission. Molecular analysis was performed by sequencing the highly variable 450 nucleotides region of the N gene (N-450) of Mv genome. Two-hundred and ninety-nine strains of Mv were analysed. The phylogenetic analysis showed five different variants, two not previously described in the studied area, belonging to D8 and B3 genotypes. Three events of continuous transmission of autochthonous variants (D8-Osaka, D8-London and B3-Milan variants) and two events of continuous transmission of imported variants (B3-Dublin and D8-Hulu Langat) tracked five different transmission pathways. These pathways outlined two epidemic peaks: the first in April and the second in July 2017. The correlation between Mv variant and the epidemiological data may enable us to identify the sources of virus importation and recognise long-lasting virus transmission pathways.

Childhood MMR vaccination and the incidence rate of measles infection: a ten year longitudinal cohort study of American children born in the 1990s.

BACKGROUND: Measles (rubeola) is a highly contagious disease with significant morbidity/mortality. Measles-Mumps-Rubella (MMR) is a live-attenuated vaccine used in the United States (US) since the early 1970s to prevent measles infection. This retrospective longitudinal cohort study examined childhood MMR vaccination effectiveness (VE) on preventing diagnosed measles cases. METHODS: The Independent Healthcare Research Database (IHRD) is composed of non-identifiable linked eligibility and claim healthcare records prospectively generated from the Florida Medicaid system. The SAS system was utilized to examine a cohort of 101,736 persons eligible for Florida Medicaid from 1990 to 2009 and continuously eligible with ≥10 outpatient office visits during the 120-month period following birth. There were 32,870 persons (224,492 person-years) in the cohort receiving a single dose of childhood MMR vaccine (vaccinated) and 43,538 persons (434,637 person-years) in an unvaccinated cohort (no exposures to measles-containing vaccine). The frequency of diagnosed measles (ICD-9 code: 055xxx) was examined. Cox proportional hazards models evaluated MMR vaccination and diagnosed measles over time. RESULTS: MMR vaccinated cohort members were at significantly reduced risk of measles in the unadjusted (VE = 83.6, 95% CI = 67.2-91.8%) and adjusted (VE = 80.7, 95% CI = 61.5-83.9%) models as compared to the unvaccinated cohort. VE = 80% among younger MMR recipients (12-15 months), whereas VE = 90% among older MMR recipients (16-20 months) as compared to the unvaccinated cohort. CONCLUSION: Routine childhood MMR vaccination significantly reduced the incidence rate of childhood measles infections, and the VE was greater in the older recipients (16-20 months) than in the younger recipients (12-15 months).

Algoritmo diagnóstico para la confirmación de casos de sarampión y rubéola en México.

Due to the successful implementation of measles and rubella elimination strategies, Mexico announced the interruption of endemic transmission of measles in 1996 and that of rubella in 2008. After a verification process, the region of the Americas was declared free of rubella and congenital rubella syndrome in 2015 and of measles in 2016. In order to maintain the elimination status in Mexico, it is essential to continue laboratory surveillance within the framework of the Global Measles and Rubella Laboratory Network. The Institute of Epidemiological Diagnosis and Reference, through the National Network of Public Health Laboratories, guarantees timely and reliable results in view of the possible reintroduction of these and other emerging pathogens.

Debido a la implementación exitosa de las estrategias de eliminación del sarampión y la rubéola, México enunció la interrupción de la transmisión endémica del sarampión en 1996 y de la rubéola en 2008. Después de un proceso de verificación, la región de las Américas fue declarada libre de rubéola y del síndrome de rubéola congénita en 2015 y del sarampión en 2016. Para mantener el estatus de eliminación en México es esencial continuar con la vigilancia por laboratorio en el marco de la Red Mundial de Laboratorios de Sarampión y Rubéola. El Instituto de Diagnóstico y Referencia Epidemiológicos, a través de la Red Nacional de Laboratorios de Salud Pública, garantiza resultados oportunos y confiables ante la posible reintroducción de estos y otros patógenos emergentes.

Improving measles incidence inference using age-structured serological data.

Measles is a target for elimination in all six WHO regions by 2020, and over the last decade, there has been considerable progress towards this goal. Surveillance is recognised as a cornerstone of elimination programmes, allowing early identification of outbreaks, thus enabling control and preventing re-emergence. Fever-rash surveillance is increasingly available across WHO regions, and this symptom-based reporting is broadly used for measles surveillance. However, as measles control increases, symptom-based cases are increasingly likely to reflect infection with other diseases with similar symptoms such as rubella, which affects the same populations, and can have a similar seasonality. The WHO recommends that cases from suspected measles outbreaks be laboratory-confirmed, to identify 'true' cases, corresponding to measles IgM titres exceeding a threshold indicative of infection. Although serological testing for IgM has been integrated into the fever-rash surveillance systems in many countries, the logistics of sending in every suspected case are often beyond the health system's capacity. We show how age data from serologically confirmed cases can be leveraged to infer the status of non-tested samples, thus strengthening the information we can extract from symptom-based surveillance. Applying an age-specific confirmation model to data from three countries with divergent epidemiology across Africa, we identify the proportion of cases that need to be serologically tested to achieve target levels of accuracy in estimated infected numbers and discuss how this varies depending on the epidemiological context. Our analysis provides an approach to refining estimates of incidence leveraging all available data, which has the potential to improve allocation of resources, and thus contribute to rapid and efficient control of outbreaks.

Global importation and population risk factors for measles in New Zealand: a case study for highly immunized populations.

As endemic measles is eliminated through immunization, countries must determine the risk factors for the importation of measles into highly immunized populations to target control measures. Despite eliminating endemic measles, New Zealand suffers from outbreaks after introductions from abroad, enabling us to use it as a model for measles introduction risk. We used a generalized linear model to analyze risk factors for 1137 measles cases from 2007 to June 2014, provide estimates of national immunity levels, and model measles importation risk. People of European ethnicity made up the majority of measles cases. Age is a positive risk factor, particularly 0-2-year-olds and 5-17-year-old Europeans, along with increased wealth. Pacific islanders were also at greater risk, but due to 0-2-year-old cases. Despite recent high measles, mumps, and rubella vaccine immunization coverage, overall population immunity against measles remains ~90% and is lower in people born between 1982 and 2005. Greatest measles importation risk is during December, and countries predicted to be sources have historical connections and highest travel rates (Australia and UK), followed by Asian countries with high travel rates and higher measles incidences. Our results suggest measles importation due to travel is seeding measles outbreaks, and immunization levels are insufficient to continue to prevent outbreaks because of heterogeneous immunity in the population, leaving particular age groups at risk.

Drivers of measles mortality: the historic fatality burden of famine in Bangladesh.

Measles is a major cause of childhood morbidity and mortality in many parts of the world. Estimates of the case-fatality rate (CFR) of measles have varied widely from place to place, as well as in the same location over time. Amongst populations that have experienced famine or armed conflict, measles CFR can be especially high, although past work has mostly focused on refugee populations. Here, we estimate measles CFR between 1970 and 1991 in a rural region of Bangladesh, which experienced civil war and famine in the 1970s. We use historical measles mortality data and a mechanistic model of measles transmission to estimate the CFR of measles. We first demonstrate the ability of this model to recover the CFR in the absence of incidence data, using simulated mortality data. Our method produces CFR estimates that correspond closely to independent estimates from surveillance data and we can capture both the magnitude and the change in CFR suggested by these previous estimates. We use this method to quantify the sharp increase in CFR that resulted in a large number of deaths during a measles outbreak in the region in 1976. Most of the children who died during this outbreak were born during a famine in 1974, or in the 2 years preceding the famine. Our results suggest that the period of turmoil during and after the 1971 war and the sustained effects of the famine, is likely to have contributed to the high fatality burden of the 1976 measles outbreak in Matlab.

Optimal vaccine schedules to maintain measles elimination with a two-dose routine policy.

Measles was eliminated in the Americas in 2002 by a combination of routine immunizations and supplementary immunization activities. Recent outbreaks underscore the importance of reconsidering vaccine policy in order to maintain elimination. We constructed an age-structured dynamical model for the distribution of immunity in a population with routine immunization and without disease, and analysed the steady state for an idealized age structure and for real age structures of countries in the Americas. We compared the level of immunity maintained by current policy in these countries to the level maintainable by an optimal policy. The optimal age target for the first routine dose of measles vaccine depends on the timing and coverage of both doses. Similarly, the optimal age target for the second dose of measles vaccine depends on the timing and coverage of the first dose. The age targets for the first and second doses of measles vaccine should be adjusted for the post-elimination era, by specifically accounting for current context, including realized coverage of both doses, and altered maternal immunity. Doing so can greatly improve the proportion immune within a population, and therefore the chances of maintaining measles elimination, without changing coverage.

Effect of socioeconomic deprivation on uptake of measles, mumps and rubella vaccination in Liverpool, UK over 16 years: a longitudinal ecological study.

Suboptimal uptake of the measles, mumps and rubella (MMR) vaccine by certain socioeconomic groups may have contributed to recent large measles outbreaks in the UK. We investigated whether socioeconomic deprivation was associated with MMR vaccine uptake over 16 years. Using immunization data for 72,351 children born between 1995 and 2012 in Liverpool, UK, we examined trends in vaccination uptake. Generalized linear models were constructed to examine the relative effect of socioeconomic deprivation and year of birth on MMR uptake. Uptake of MMR1 by age 24 months ranged between 82·5% in 2003 [95% confidence interval (CI) 81·2-83·7] and 93·4% in 2012 (95% CI 92·7-94·2). Uptake of MMR2 by age 60 months ranged between 65·3% (95% CI 64·4-67·4) in 2006 and 90·3% (95% CI 89·4-91·2) in 2012. In analysis adjusted for year of birth and sex, children in the most deprived communities were at significantly greater risk of not receiving MMR1 [risk ratio (RR) 1·70, 95% CI 1·45-1·99] and MMR2 (RR 1·36, 95% CI 1·22-1·52). Higher unemployment and lower household income were significantly associated with low uptake. Contrary to concerns about lower MMR uptake in affluent families, over 16 years, children from the most socioeconomically deprived communities have consistently had the lowest MMR uptake. Targeted catch-up campaigns and strategies to improve routine immunization uptake in deprived areas are needed to minimize the risk of future measles outbreaks.

Catching measles in an appropriately vaccinated group: a well-circumscribed outbreak in the South East of Ireland, September-November 2013.

A measles outbreak occurred in a school in a small town in the South East of Ireland in September-November 2013. Most (and all early) cases had one dose of the measles-mumps- rubella (MMR) vaccination. All suspected cases were followed up, in order to advise on sampling and provide public health advice to them and their contacts. MMR vaccination control measures were instituted in the town. These included early second MMR in primary schools and childcare facilities, bringing forward the planned school MMR catch-up programme, early first MMR dose for children aged 6-12 months and targeted advice to unvaccinated children. There were 20 cases (17 confirmed) of measles associated with the outbreak. Fifteen cases occurred in the index school, with four in pre-school-age children (<4 years) who had clear epidemiological links with children at the school. This was a well-circumscribed outbreak occurring, unusually, in a well-vaccinated population. The outbreak came late to the attention of Department of Public Health staff but prompt action, once notified, and institution of control measures resulted in quick termination of the outbreak and prevention of cases in a neighbouring city.

Prevention of measles spread on a paediatric ward.

Since measles is a highly contagious respiratory infection with significant airborne transmission risk in hospitals, effective prevention measures are crucial. After a mother accompanying her child on a paediatric ward lacking a negative pressure room was diagnosed with measles, exposed persons without evidence of immunity (documentary evidence of receiving two doses of measles-mumps-rubella vaccine) were treated with vaccination or intravenous immunoglobulin (IVIG). The interruption of transmission with these treatments was evaluated. There were 44 children and 101 adults exposed to the index patient. Twenty-five children and 88 adults were considered immune, providing evidence of immunity. Nineteen children and 13 adults were either given vaccination or IVIG for post-exposure prophylaxis (PEP). There were no additional cases of measles after 3 weeks follow-up. We conclude that measles is highly preventable by adequate PEP with vaccination or IVIG in a healthcare setting that lacks the benefit of a negative pressure room.

Age-specific measles mortality during the late 19th-early 20th centuries.

Measles mortality fell prior to the introduction of vaccines or antibiotics. By examining historical mortality reports we sought to determine how much measles mortality was due to epidemiological factors such as isolation from major population centres or increased age at time of infection. Age-specific records were available from Aberdeen; Scotland; New Zealand and the states of Australia at the end of the 19th and beginning of the 20th centuries. Despite the relative isolation of Australia, measles mortality was concentrated in very young children similar to Aberdeen. In the more isolated states of Tasmania, Western Australia and Queensland adults made up 14-15% of measles deaths as opposed to 8-9% in Victoria, South Australia and New South Wales. Mortality in Iceland and Faroe Islands during the 1846 measles epidemic was used as an example of islands isolated from respiratory pathogens. The transition from crisis mortality across all ages to deaths concentrated in young children occurred prior to the earliest age-specific mortality data collected. Factors in addition to adult age of infection and epidemiological isolation such as nutritional status and viral virulence may have contributed to measles mortality outcomes a century ago.

Immunity to polio, measles and rubella in women of child-bearing age and estimated congenital rubella syndrome incidence, Cambodia, 2012.

Significant gaps in immunity to polio, measles, and rubella may exist in adults in Cambodia and threaten vaccine-preventable disease (VPD) elimination and control goals, despite high childhood vaccination coverage. We conducted a nationwide serological survey during November-December 2012 of 2154 women aged 15-39 years to assess immunity to polio, measles, and rubella and to estimate congenital rubella syndrome (CRS) incidence. Measles and rubella antibodies were detected by IgG ELISA and polio antibodies by microneutralization testing. Age-structured catalytic models were fitted to rubella serological data to predict CRS cases. Overall, 29.8% of women lacked immunity to at least one poliovirus (PV); seroprevalence to PV1, PV2 and PV3 was 85.9%, 93.4% and 83.3%, respectively. Rubella and measles antibody seroprevalence was 73.3% and 95.9%, respectively. In the 15-19 years age group, 48.2% [95% confidence interval (CI) 42.4-54.1] were susceptible to either PV1 or PV3, and 40.3% (95% CI 33.0-47.5) to rubella virus. Based on rubella antibody seroprevalence, we estimate that >600 infants are born with CRS in Cambodia annually. Significant numbers of Cambodian women are still susceptible to polio and rubella, especially those aged 15-19 years, emphasizing the need to include adults in VPD surveillance and a potential role for vaccination strategies targeted at adults.