Jeanette J. Rainey

Reasons related to non-vaccination and under-vaccination of children in low and middle income countries: Findings from a systematic review of the published literature, 1999–2009

OBJECTIVE Despite increases in routine vaccination coverage during the past three decades, the percent of children completing the recommended vaccination schedule remains below expected targets in many low and middle income countries. In 2008, the World Health Organization Strategic Advisory Group of Experts on Immunization requested more information on the reasons that children were under-vaccinated (receiving at least one but not all recommended vaccinations) or not vaccinated in order to develop effective strategies and interventions to reach these children. METHODS A systematic review of the peer-reviewed literature published from 1999 to 2009 was conducted to aggregate information on reasons and factors related to the under-vaccination and non-vaccination of children. A standardized form was used to abstract information from relevant articles identified from eight different medical, behavioural and social science literature databases. FINDINGS Among 202 relevant articles, we abstracted 838 reasons associated with under-vaccination; 379 (45%) were related to immunization systems, 220 (26%) to family characteristics, 181 (22%) to parental attitudes and knowledge, and 58 (7%) to limitations in immunization-related communication and information. Of the 19 reasons abstracted from 11 identified articles describing the non-vaccinated child, 6 (32%) were related to immunization systems, 8 (42%) to parental attitudes and knowledge, 4 (21%) to family characteristics, and 1 (5%) to communication and information. CONCLUSIONS Multiple reasons for under-vaccination and non-vaccination were identified, indicating that a multi-faceted approach is needed to reach under-vaccinated and unvaccinated children. Immunization system issues can be addressed through improving outreach services, vaccine supply, and health worker training; however, under-vaccination and non-vaccination linked to parental attitudes and knowledge are more difficult to address and likely require local interventions.

Spatial distribution of Burkitt’s lymphoma in Kenya and association with malaria risk

Endemic Burkitt’s lymphoma (BL) is the most common paediatric malignancy in equatorial Africa and was originally shown to occur at high‐incidence rates in regions where malaria transmission is holoendemic. New ecological models of malaria that are based on both parasite prevalence and disease have been described. In this study, we examined district level data collected from paediatric BL cases in Kenya from 1988 through 1997 and assessed whether the distribution of district level incidence rates could be explained by new ecologic estimates of malaria risk. Chi‐square tests and log‐linear regression models were used to evaluate these associations. An association with tribe of origin as a factor also was examined. The 10‐year average annual incidence rate (IR) for Kenya was 0.61 per 100 000 children. Incidence rates varied by malaria transmission intensity as follows: low malaria risk (BL IR = 0.39), arid/seasonal (0.25), highland (0.66), endemic coast (0.68), and endemic lake (1.23) (χ2 = 11.32, P = 0.002). In a log‐linear model, BL rates were 3.5 times greater in regions with chronic and intense malaria transmission intensity than in regions with no or sporadic malaria transmission (odds ratio = 3.47, 95% confidence interval = 1.30–9.30), regardless of tribe. Although crude tribe‐specific incidence rates ranged between 0.0 and 3.26, tribe was not associated with BL after controlling for malaria. These findings support the aetiologic role of intense malaria transmission intensity in BL.

Spatial clustering of endemic Burkitt's lymphoma in high-risk regions of Kenya

Endemic Burkitts lymphoma (eBL), the most common childhood cancer in sub‐Saharan Africa, occurs at a high incidence in western Kenya, a region that also experiences holoendemic malaria. Holoendemic malaria has been identified as a co‐factor in the etiology of this cancer. We hypothesized that eBL may cluster spatially within this region. Medical records for all eBL cases diagnosed from 1999 through 2004 at Nyanza Provincial General Hospital were reviewed for case residential information to examine this hypothesis. Two cluster detection methods, Anselins Local Moran test for spatial autocorrelation and a spatial scan test statistic, were applied to this residential data to determine whether statistically significant high‐ and low‐risk areas were present in the Province. During the 6‐year study period, 272 children were diagnosed with eBL, with an average annual incidence of 2.15 cases per 100,000 children. Using Empirical Bayes smoothed rates, the Local Moran test identified 1 large multi‐centered area of low eBL risk (p‐values < 0.01) and 2 significant multi‐centered clusters of high eBL risk (p‐values < 0.001). The spatial scan detected 3 small independent low‐risk areas (p‐values < 0.02) and 2 high‐risk clusters (p‐values = 0.001), both similar in location to those identified from the Local Moran analysis. Significant spatial clustering of elevated eBL risk in high‐malaria transmission regions and of reduced incidence where malaria is infrequent suggests that malaria plays a role in the complex eBL etiology, but that additional factors are also likely involved.

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.

Uptake of oral rotavirus vaccine and timeliness of routine immunization in Brazil's National Immunization Program.

INTRODUCTION In March, 2006, oral rotavirus vaccine was added to Brazils infant immunization schedule with recommended upper age limits for initiating (by age 14 weeks) and completing (by age 24 weeks) the two-dose series to minimize age-specific risk of intussusception following rotavirus vaccination. Several years after introduction, estimated coverage with rotavirus vaccine (83%) was lower compared to coverage for other recommended childhood immunizations (≥94%). METHODS We analyzed data from Brazils national immunization program on uptake of oral rotavirus vaccine by geographic region and compared administrative coverage estimates for first and second doses of oral rotavirus vaccine (Rota1 and Rota2) with first and second doses of diphtheria-tetanus-pertussis-Haemophilus influenzae type b vaccine (DTP-Hib1 and DTP-Hib2). For 27 Brazilian cities, we compared differences between estimated rotavirus and DTP-Hib coverage in 2010 with delayed receipt of DTP-Hib vaccine among a cohort of children surveyed before rotavirus introduction. RESULTS In 2010, infant vaccination coverage was 99.0% for DTP-Hib1 versus 95.2% for Rota1 (3.8% difference), and 98.4% for DTP-Hib2 versus 83.0% for Rota2 (15.4% difference), with substantial regional variation. Differences between DTP-Hib and rotavirus vaccination coverage in Brazilian cities correlated with delay in DTP-Hib vaccination among children surveyed. Age restrictions for initiating and completing the rotavirus vaccination series likely contributed to lower coverage with rotavirus vaccine in Brazil. CONCLUSION To maximize benefits of rotavirus vaccination, strategies are needed to improve timeliness of routine immunizations; monitoring rotavirus vaccine uptake and intussusception risk is needed to guide further recommendations for rotavirus vaccination.

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.

Vaccination Coverage in Haiti: Results from the 2009 National Survey

INTRODUCTION Since 1977, vaccinations to protect against tuberculosis, diphtheria, tetanus, pertussis, polio, and measles (and rubella since 2009) have been offered to children in Haiti through the routine immunization program. From April to July 2009, a national vaccination coverage survey was conducted to assess the success of the routine immunization program at reaching children in Haiti. METHODS A multi-stage cluster survey was conducted using a modified WHO method for household sampling. A standardized questionnaire was administered to collect vaccination histories, demographic information, and reasons for under-vaccination of children aged 12-23 months. A child who received the eight recommended routine vaccinations was considered fully vaccinated. The routine vaccination schedule was used to define valid doses and estimate the percentage of children vaccinated on time. RESULTS Among 1345 children surveyed, 40.4% (95% CI: 36.6-44.2) of the 840 children with vaccination cards had received all eight recommended vaccinations. Coverage was highest for the Bacille Calmette-Guérin vaccine (87.3%), the first doses of the diphtheria-tetanus-pertussis vaccine (92.0%), and oral poliovirus vaccine (93.4%) and lowest for measles vaccine (46.9%). Timely vaccination rates were lower. Assuming similar coverage for the 505 children without cards, coverage with the complete vaccination series among all surveyed children 31.9%. Reasons for under-vaccination included not having enough time to reach the vaccination location (24.8%), having a child who was ill (13.8%), and not knowing when, or forgetting, to go for vaccination (12.8%). CONCLUSIONS AND RECOMMENDATIONS Coverage for early-infant vaccines was high; however, most children did not complete the full vaccination series, and many children received vaccinations later than recommended. Efforts to improve the immunization program should include increasing the frequency of outreach services, training for vaccination staff to minimize missed opportunities, and better communicating the timing of vaccinations to encourage caregivers to bring their children for vaccinations at the recommended age. Efforts to promote the benefits of vaccination and card retention are also needed.

Vaccination with Haemophilus influenzae type b conjugate vaccine reduces bacterial meningitis in Morocco

INTRODUCTION Haemophilus influenzae type b (Hib) is a leading cause of bacterial meningitis and pneumonia and can be prevented by Hib vaccine. We conducted a vaccine impact evaluation to support continued use of Hib vaccine in Morocco following introduction in 2007. METHODS Bacterial meningitis surveillance data from 2004 to 2009 were obtained from 11 sentinel hospitals located in eight provinces and one prefecture in Morocco to examine Hi meningitis reporting for cases aged <5 years. We defined the years of 2004-2006 as the pre-vaccine period and 2008-2009 as the post-vaccine period and compared the mean annual number of confirmed Hi meningitis cases for these time periods using a Chi-square test. We calculated the minimum incidence of Hi meningitis during the evaluation period in Grand Casa Prefecture, where the catchment population could be estimated. RESULTS From 2004 to 2009, 1844 suspected meningitis case-patients aged <5 years were reported; 354 (19.2%) were confirmed with bacterial meningitis, including 105 (29.7%) Hi cases. The mean annual number of confirmed Hi meningitis cases decreased by 75%, from 24 in the pre-vaccine period to 6 during the post-vaccine period (p<0.001). Assuming Hi cases with unknown age were <5 years of age, the estimated minimum incidence of confirmed Hi meningitis in Grand Casa Prefecture decreased by 93%, from 15 cases per 100,000 children in the pre-vaccine period to 1 case per 100,000 children in the post-vaccine period. CONCLUSION Hib vaccine introduction likely significantly reduced the occurrence of Hi meningitis among children aged <5 years at the 11 sentinel hospitals included in this evaluation in Morocco, suggesting that continued use of Hib vaccine in Morocco would be beneficial.

Measles Elimination in the Americas: A Comparison Between Countries With a One-Dose and Two-Dose Routine Vaccination Schedule

BACKGROUND The Region of the Americas eliminated measles in 2002 through high first-dose routine measles vaccine coverage and vaccination campaigns every 4-6 years; a second routine dose at school entry was added in some countries. The impact of this second routine dose on measles elimination was evaluated. METHODS Data on socioeconomic factors, demographic characteristics, vaccination coverage, and the estimated proportion of children (<15 years of age) susceptible to measles were compiled. Countries were grouped using propensity score methods, and Kaplan-Meier curves were used to compare time to measles elimination between countries with a 1-dose schedule and those with a 2-dose schedule. RESULTS One-dose (n = 14) and 2-dose (n = 7) countries did not differ with respect to median routine first-dose measles vaccine coverage, median coverage for 3 measles campaigns, or estimated percentage of susceptible children after routine first vaccination dose and campaigns. Compared with 1-dose countries, 2-dose countries had higher median gross national income per capita (P = .002), percentage of population living in urban areas (P = .04), and female literacy (P = .01), as well as lower infant mortality (P = .007); however, no differences in time to elimination were found. CONCLUSIONS One-dose and 2-dose countries had similar times to measles elimination despite socioeconomic differences between their populations. A second routine dose might not have hastened measles elimination, because threshold immunity needed to eliminate measles was achieved with high first routine dose coverage and vaccination campaigns. Further research will be needed to determine the applicability of these findings to other regions.