Amra Uzicanin

Field Effectiveness of Live Attenuated Measles-Containing Vaccines: A Review of Published Literature

BACKGROUND Information on measles vaccine effectiveness (VE) is critical to help inform policies for future global measles control goals. METHODS We reviewed results of VE studies published during 1960-2010. RESULTS Seventy papers with 135 VE point estimates were identified. For a single dose of vaccine administered at 9-11 months of age and ≥12 months, the median VE was 77.0% (interquartile range [IQR], 62%-91%) and 92.0% (IQR, 86%-96%), respectively. When analysis was restricted to include only point estimates for which vaccination history was verified and cases were laboratory confirmed, the median VE was 84.0% (IQR, 72.0%-95.0%) and 92.5% (IQR, 84.8%-97.0%) when vaccine was received at 9-11 and ≥12 months, respectively. Published VE vary by World Health Organization region, with generally lower estimates in countries belonging to the African and SouthEast Asian Regions. For 2 doses of measles-containing vaccine, compared with no vaccination, the median VE was 94.1% (IQR, 88.3%-98.3%). CONCLUSIONS The VE of the first dose of measles-containing vaccine administered at 9-11 months was lower than what would be expected from serologic evaluations but was higher than expected when administered at ≥12 months. The median VE increased in a subset of articles in which classification bias was reduced through verified vaccination history and laboratory confirmation. In general, 2 doses of measles-containing vaccine provided excellent protection against measles.

Changing Epidemiology of Measles in Africa

BACKGROUND In Africa before the introduction of measles vaccination, measles primarily affected young children. To describe measles epidemiology in Africa since the start of accelerated measles control activities in 2001, we analyzed regional measles case-based surveillance data for 2002-2009. METHODS Country-years were grouped by 10-year moving average of routine measles vaccination coverage (aMCV1). Age was log transformed, and pair-wise comparisons of means were made. A χ(2) test was used to assess association between coverage and age groups. Cumulative percent curves and percentiles of age, dot plots with Loess curve, and Spearman rank correlation coefficient were calculated. RESULTS Of 180,284 suspected cases, 73,009 (41%) were confirmed as measles. Of these, the mean age was 79 months (median, 36 months; interquartile range, 16-96 months) and significantly younger in country-years with <50% aMCV1 than those with 50%-74% aMCV1 (P=.03) and ≥75% (P=.02). With increasing coverage, there was a slight decrease in age in the 10th and 25th and moderate increase in age in the 50th, 75th, and 90th percentiles. CONCLUSIONS During 2002-2009, the median age of confirmed measles was 36 months. In countries with ≥50% aMCV1 coverage compared with low-coverage countries, age shifted to older children and young adults; for infants, age decreased slightly with higher coverage.

Positive network assortativity of influenza vaccination at a high school: implications for outbreak risk and herd immunity

Schools are known to play a significant role in the spread of influenza. High vaccination coverage can reduce infectious disease spread within schools and the wider community through vaccine-induced immunity in vaccinated individuals and through the indirect effects afforded by herd immunity. In general, herd immunity is greatest when vaccination coverage is highest, but clusters of unvaccinated individuals can reduce herd immunity. Here, we empirically assess the extent of such clustering by measuring whether vaccinated individuals are randomly distributed or demonstrate positive assortativity across a United States high school contact network. Using computational models based on these empirical measurements, we further assess the impact of assortativity on influenza disease dynamics. We found that the contact network was positively assortative with respect to influenza vaccination: unvaccinated individuals tended to be in contact more often with other unvaccinated individuals than with vaccinated individuals, and these effects were most pronounced when we analyzed contact data collected over multiple days. Of note, unvaccinated males contributed substantially more than unvaccinated females towards the measured positive vaccination assortativity. Influenza simulation models using a positively assortative network resulted in larger average outbreak size, and outbreaks were more likely, compared to an otherwise identical network where vaccinated individuals were not clustered. These findings highlight the importance of understanding and addressing heterogeneities in seasonal influenza vaccine uptake for prevention of large, protracted school-based outbreaks of influenza, in addition to continued efforts to increase overall vaccine coverage.

How should social mixing be measured: comparing web-based survey and sensor-based methods

BackgroundContact surveys and diaries have conventionally been used to measure contact networks in different settings for elucidating infectious disease transmission dynamics of respiratory infections. More recently, technological advances have permitted the use of wireless sensor devices, which can be worn by individuals interacting in a particular social context to record high resolution mixing patterns. To date, a direct comparison of these two different methods for collecting contact data has not been performed.MethodsWe studied the contact network at a United States high school in the spring of 2012. All school members (i.e., students, teachers, and other staff) were invited to wear wireless sensor devices for a single school day, and asked to remember and report the name and duration of all of their close proximity conversational contacts for that day in an online contact survey. We compared the two methods in terms of the resulting network densities, nodal degrees, and degree distributions. We also assessed the correspondence between the methods at the dyadic and individual levels.ResultsWe found limited congruence in recorded contact data between the online contact survey and wireless sensors. In particular, there was only negligible correlation between the two methods for nodal degree, and the degree distribution differed substantially between both methods. We found that survey underreporting was a significant source of the difference between the two methods, and that this difference could be improved by excluding individuals who reported only a few contact partners. Additionally, survey reporting was more accurate for contacts of longer duration, and very inaccurate for contacts of shorter duration. Finally, female participants tended to report more accurately than male participants.ConclusionsOnline contact surveys and wireless sensor devices collected incongruent network data from an identical setting. This finding suggests that these two methods cannot be used interchangeably for informing models of infectious disease dynamics.

What Will It Take to Achieve Measles Elimination in the World Health Organization European Region: Progress From 2003–2009 and Essential Accelerated Actions

BACKGROUND The Member States of the European Region (EUR) of the World Health Organization (WHO) have made great progress towards achieving the goal of measles elimination by 2010. METHODS Measles surveillance and vaccine coverage data from 2003-2009 reported to WHO were analyzed. A review of feasibility of reaching the elimination goal by the 2010 target date was conducted in 2009. RESULTS From 2003-2009, the measles incidence decreased dramatically and coverage with 2 doses of measles vaccine increased among wide age groups of susceptible persons. With the decrease of disease incidence and the reduction of outbreaks in the eastern part of EUR, the proportion of reported cases in the western part increased. In 2009, outbreaks in 5 countries accounted for 89.6% of reported cases. Challenges to reach the 2010 goal include ongoing outbreaks with reestablished endemicity in some countries, decreased demand for vaccines with an increased focus on the measles vaccine safety, and population groups with limited access to immunization services. CONCLUSIONS Measles elimination in EUR is attainable, albeit not by 2010. EUR countries should ensure political commitment and resources to protect the gains made to date and address these challenges to sustain the progress and achieve the elimination goal.

Dried Blood Spots on Filter Paper as an Alternative Specimen for Measles Diagnostics: Detection of Measles Immunoglobulin M Antibody by a Commercial Enzyme Immunoassay

BACKGROUND We compared the results of a serum-based measles immunoglobulin M (IgM) test with results of tests using paired reconstituted dried filter paper blood spot (DBS) samples to assess the feasibility of using DBS samples for measles diagnostic procedures. METHODS We collected 588 paired serum and DBS samples from 349 children aged 8 months through 12 years at Mulago Hospital in Kampala, Uganda; of these samples, 513 (87%) were collected from children with a clinical diagnosis of measles 0-33 days after rash, and 75(13%) were collected from children hospitalized for other reasons. Eluted DBS and serum samples were tested using a commercial measles IgM enzyme immunoassay. Detection of viral RNA was attempted on a subset of 20 DBS by reverse-transcriptase polymerase chain reaction. RESULTS Among the 513 sample pairs collected from children with measles, the concordances for samples collected during days 0-6 and >1 week after rash were 95.7% and 100%, respectively (P<.01). The relative sensitivity and specificity of the DBS-based assay during the first week were 98.7% and 88.9%, respectively, and the sensitivity and specificity >1 week after rash were 100% and 100%, respectively. Viral RNA was detected in 5 (26%) of 19 DBS samples tested. Among 75 sample pairs collected from children hospitalized for other reasons, concordance was 94.7%. CONCLUSIONS DBS samples are a feasible alternative sample for measles diagnostic procedures in high-incidence settings.

The role of heterogeneity in contact timing and duration in network models of influenza spread in schools

Influenza poses a significant health threat to children, and schools may play a critical role in community outbreaks. Mathematical outbreak models require assumptions about contact rates and patterns among students, but the level of temporal granularity required to produce reliable results is unclear. We collected objective contact data from students aged 5–14 at an elementary school and middle school in the state of Utah, USA, and paired those data with a novel, data-based model of influenza transmission in schools. Our simulations produced within-school transmission averages consistent with published estimates. We compared simulated outbreaks over the full resolution dynamic network with simulations on networks with averaged representations of contact timing and duration. For both schools, averaging the timing of contacts over one or two school days caused average outbreak sizes to increase by 1–8%. Averaging both contact timing and pairwise contact durations caused average outbreak sizes to increase by 10% at the middle school and 72% at the elementary school. Averaging contact durations separately across within-class and between-class contacts reduced the increase for the elementary school to 5%. Thus, the effect of ignoring details about contact timing and duration in school contact networks on outbreak size modelling can vary across different schools.

Measles outbreak in Burkina Faso, 2009: A case–control study to determine risk factors and estimate vaccine effectiveness

OBJECTIVE We investigated a large measles outbreak that occurred in 2009 in Burkina Faso in order to describe the epidemic, assess risk factors associated with measles, and estimate measles vaccine effectiveness. METHODS We reviewed national surveillance and measles vaccine coverage data, and conducted a case-control study in three geographic areas. Case-patients were randomly selected from the national case-based measles surveillance database or, when a case-patient could not be traced, were persons in the same community who experienced an illness meeting the WHO measles clinical case definition. Controls were matched to the same age stratum (age 1-14 years or age 15-30 years) and community as case-patients. Risk factors were assessed using conditional logistic regression. RESULTS Lack of measles vaccination was the main risk factor for measles in all three geographic areas for children aged 1-14 years (adjusted matched odds ratio [aMOR] [95% confidence interval (CI)], 19.4 [2.4-155.9], 5.9 [1.6-21.5], and 6.4 [1.8-23.0] in Bogodogo, Zorgho, and Sahel, respectively) and persons aged 15-30 years (aMOR [95% CI], 3.2 [1.1-9.7], 19.7 [3.3-infinity], 8.0 [1.8-34.8] in Bogodogo, Zorgho, and Sahel, respectively). Among children aged 1-14 years, VE of any measles vaccination prior to 2009 was 94% (95% CI, 45-99%) in Bogodogo, 87% (95% CI, 37-97%) in Zorgho, and 84% (95% CI, 41-96%) in Sahel. Main reasons for not receiving measles vaccination were lack of knowledge about vaccination campaigns or need for measles vaccination and absence during vaccination outreach or campaign activities. CONCLUSION These results emphasize the need for improved strategies to reduce missed opportunities for vaccination and achieve high vaccination coverage nationwide in order to prevent large measles outbreaks and to continue progress toward measles mortality reduction.

School closures during the 2009 influenza pandemic: national and local experiences

BackgroundSchool closure is a non-pharmaceutical intervention that was considered in many national pandemic plans developed prior to the start of the influenza A(H1N1)pdm09 pandemic, and received considerable attention during the event. Here, we retrospectively review and compare national and local experiences with school closures in several countries during the A(H1N1)pdm09 pandemic. Our intention is not to make a systematic review of country experiences; rather, it is to present the diversity of school closure experiences and provide examples from national and local perspectives.MethodsData were gathered during and following a meeting, organized by the European Centres for Disease Control, on school closures held in October 2010 in Stockholm, Sweden. A standard data collection form was developed and sent to all participants. The twelve participating countries and administrative regions (Bulgaria, China, France, Hong Kong Special Administrative Region (SAR), Italy, Japan, New Zealand, Serbia, South Africa, Thailand, United Kingdom, and United States) provided data.ResultsOur review highlights the very diverse national and local experiences on school closures during the A(H1N1)pdm09 pandemic. The processes including who was in charge of making recommendations and who was in charge of making the decision to close, the school-based control strategies, the extent of school closures, the public health tradition of responses and expectations on school closure varied greatly between countries. Our review also discusses the many challenges associated with the implementation of this intervention and makes recommendations for further practical work in this area.ConclusionsThe single most important factor to explain differences observed between countries may have been the different public health practises and public expectations concerning school closures and influenza in the selected countries.

Poliomyelitis outbreaks in Angola genetically linked to India: risk factors and implications for prevention of outbreaks due to wild poliovirus importations.

We conducted an investigation of two outbreaks of poliomyelitis in Angola during 2007-2008 due to wild poliovirus (WPV) genetically linked to India. A case-control study including 27 case-patients and 76 age- and neighborhood-matched control-subjects was conducted to assess risk factors associated with paralytic poliomyelitis, and epidemiologic links to India were explored through in-depth case-patient interviews. In multivariable analysis, case-patients were more likely than control-subjects to be undervaccinated with fewer than four routine doses of oral poliovirus vaccine (adjusted matched odds ratio [aMOR], 4.1; 95% confidence interval [CI], 1.2-13.6) and have an adult household member who traveled outside the province of residence in the 2 months preceding onset of paralysis (aMOR, 3.2; 95% CI, 1.2-8.6). No epidemiologic link with India was identified. These findings underscore the importance of routine immunization to prevent outbreaks following WPV importations and suggest a possible role of adults in sustaining WPV transmission.