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Determination of factors affecting the vaccination status of children aged 12–35 months in Lao People’s Democratic Republic

Vaccines are one of the most important achievements in public health, and a major contributor to this success is the Expanded Programme on Immunization. The utilisation of vaccination services and completion of the recommended schedule are determined by numerous factors. In Lao People’s Democratic Republic (Lao PDR), the overall immunisation coverage has been improving. However, notwithstanding the improvement in immunisation coverage and the supplementary immunisation activities, there have been measles, diphtheria, and polio outbreaks in the country. The recent multicounty study of household health surveys revealed that the within-country economic-related inequality in the delivery of a vaccine was still high in Lao PDR. Our previous work evaluated the factors associated with vaccination status among the children aged 5–9 years old, which was older age group for this type of study. This study evaluated factors that affect vaccination status among children aged between 12 and 35 months. It is a nationwide population-based cross-sectional study that used data obtained through multistage cluster sampling. We found that the proportion of infants who were fully immunised was lower than the national target and that “maternal ethnicity” (odds ratio (OR) 0.34, 95% confidence interval [CI]: 0.20–0.60), “paternal education” (OR 1.87, 95% CI: 1.12–3.10), and “source of information about vaccination date by medical staff” (OR 1.65, 95% CI: 1.01–2.71) were significantly associated with the children’s vaccination status. Numerous factors are associated with the completion of the recommended vaccine schedule, and some factors are location-specific. Identification of these factors should lead to actions for facilitating the optimal use of vaccination services by all the children in Lao PDR.


Introduction
Vaccination is considered one of the most important and cost-effective public health services for children [1,2,3,4,5,6,7,8,9,10]. Significant progress has been made towards the development of effective national immunisation programmes, and the major contributor to this success is the Expanded Programme on Immunization (EPI) of the World Health Organization (WHO), United Nations Children's Fund (UNICEF), and Global Alliance Vaccine Initiative (GAVI) [6].
The EPI was launched in 1974 as a worldwide alliance of collaborating nations whose goal was to expand immunisation services and coverage in order to save children from life-threatening, disabling vaccine-preventable diseases [6,11]. The EPI has contributed to improvements in coverage; however, the proportion of children completing the recommended vaccination schedule has not increased as anticipated [4,8,12]. The identification of factors resulting in the failure to vaccinate or to complete the vaccination schedule is important in order to achieve the EPI targets [13,14]. The utilisation of vaccination services and completion of the recommended schedule are determined by numerous factors [5, 11, 15, 16, 17, program managers through established interventions as follows: training of health workers to reduce missed opportunities, strategies to improve communication, and the enhancement of outreach services to remove barriers to vaccination [8,24].
However, other factors such as parental education, cultural mores, and the role of gender and religious beliefs are complex, country-or region-specific, and difficult to interpret [8,20,23]. Thus, location-specific enquiry is required to address factors related to the failure to vaccinate or complete vaccination schedules [23,25].
The EPI was initiated in Lao People's Democratic Republic (Lao PDR) in 1979 [26]. Immunisation coverage had improved in that measles (MCV1) immunisation coverage was 87%, diphtheria tetanus toxoid and pertussis (DTP3) immunisation coverage was 88%, tuberculosis (BCG) immunisation coverage was 82%, and polio (OPV3) immunisation coverage was 88% in 2014 [27]. The country experienced measles outbreaks between 2012 and 2014, diphtheria outbreaks between 2012 and 2013, and polio outbreaks between 2015 and 2016, despite an improvement in immunisation coverage and several supplementary immunisation activities [28]. The recent multicounty study of household health surveys revealed that Lao PDR was one of the countries where the within-country economic-related inequality in the delivery of three doses of the combined DTP vaccine was highest [10]. The reasons for failing to vaccinate or complete the vaccination schedule need to be studied in order to achieve optimal use of the vaccination services by all the children in Lao PDR and to achieve the national goal of ensuring that at least 95% of infants are fully vaccinated by 2025 [29]. Previously, we have studied the factors associated with the vaccination status among the children aged between 5 and 9 years old [30]. The aim of this study was to identify factors associated with vaccination status among children aged between 12 and 35 months which is normal target population for investigating the factors.

Study location and population
Lao PDR is a landlocked country in Southeast Asia, bordered by five countries, namely Burma, China, Vietnam, Cambodia, and Thailand. The latest data from the WHO showed that its population was approximately 6.7 million (2013) and the under-5-year-old mortality rate was 71 per 1,000 live births (2012) [31].

Sampling and sampling frame
The study was conducted to fulfil the following two objectives: 1) to estimate population-based measles and rubella immunity, and 2) to identify factors associated with the vaccination status of the cohort. The sample size was calculated based on the expected measles and rubella IgG sero-prevalence, level of confidence interval, margin of error, design effect, and loss to follow-up. The results of the investigation on first objective will be reported elsewhere. Twentysix districts were randomly selected by using probability proportional to size from 143 districts, resulting in ten provinces out of seventeen provinces and one municipality, which are scattered all over the country; moreover, two villages were randomly selected from each district using the same sampling strategy as that used for the selection of districts. Eight children (aged between 12 and 35 months) and their caretakers were randomly selected after listing all the candidates in each selected village.
For this study, 416 pairs of children and their caretakers were recruited and assessed for eligibility. Of these pairs, 15 were excluded because the children were aged <12 months or >35 months. A further 84 pairs were excluded because they did not have any vaccination record such as vaccination cards or mother and child handbooks. Finally, data from 317 pairs of children and their caretakers were analysed in this study.
In Lao PDR, the vaccination cards or mother and child handbooks are provided to children who receive any vaccination regulated by the Lao PDR Ministry of Health. Vaccination dates were transcribed from the vaccination cards or mother and child handbooks. Where vaccination dates were inaccurately recorded or not recorded, vaccinations were considered as not given. Each child's vaccination record was checked against the recommended EPI immunisation schedule [32]. Table 1 shows the immunisation schedule in Lao PDR. The following categories were used: fully immunised, if the "standard six" antigens-BCG, DTP3 (3 doses), OPV3 (3 doses), and measles vaccines-had been given by the day of interview; and partially immunised, if at least one recommended vaccine dose had not been given [19,26,33]. This study compared children who completed their standard vaccinations (fully immunised/vaccinated) with children who had not completed their vaccinations (partially immunised/vaccinated) at the time of the survey.

Statistical analysis
Bivariate analysis was performed to assess the relationship between vaccination status and factors relevant to vaccination status. The chi-square test was used for categorical variables, and the Student's t test was used for continuous variables. Crude odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by using logistic regression. Multivariate analysis was performed, and the criterion for selecting the independent variables included in the multivariate analysis was the significant level of association with vaccination status in the bivariate analysis (p < 0.1). This did not apply to the following variables: "source of information of vaccination (radio/TV)", "source of information of vaccination date (family member/friend)", and "source of information of vaccination date (radio/TV)", as the number of subjects per category was zero. The variable "paternal ethnicity" was excluded from the final multivariate logistic regression model, as it showed the highest multicollinearity among the variables in the model (variance inflation factor: VIF > 10). Backward stepwise selection was applied with the level of significance for variables to remain in the final model set at 0.05. A P value of <0.05 was considered statistically significant. Stata version 11.0/14.0 was used to perform all the statistical analyses.

Ethical considerations
The survey was reviewed and approved by the ethical committee of the Ministry of Health, Lao PDR (025NECHR), and the institutional review board of the National Center for Global Health and Medicine, Japan (NCGM-G-001459-00). Access to selected households was granted by the Ministry of Health and the provincial and district government authorities. outside the target age range, those who did not have any records for vaccination, and those for whom data regarding possession of vaccination records were unknown.

Study profile of all the subjects
Among the eligible study subjects, the proportion of children holding a vaccination card or a mother and child handbook, or both was 39.1%, 36.6%, and 24.3%, respectively. In total, 187 children (59%) were fully immunised and 130 children (41%) were partially immunised. The multivariate logistic regression model revealed that "maternal ethnicity" (OR 0.34, 95% CI: 0.20-0.60), "paternal education" (OR 1.87, 95% CI: 1.12-3.10), and "source of information about vaccination date by medical staff" (OR 1.65, 95% CI:

Factors associated with vaccination status
1.01-2.71) were significantly associated with full vaccination status (Table 5).

Discussion
This study found that 187 children (59%) were fully immunised and 130 children (41%) were partially immunised. It also identified factors associated with the

Family characteristic-related factors
Rainey et al. found that family characteristics relevant to vaccination status included caretaker ethnicity, socio-economic status, and education level [8].
Caretaker age is not mentioned in the list compiled by Rainey et al. but is often described as one of the risk factors for the vaccination status of the children, particularly maternal age. However, the association between childhood vaccination status and maternal age is controversial in the literature [5,6,8,22,24,33]. Our previous study conducted among the children aged 5-9 years old has shown that full vaccination increases with maternal age [30]. This study showed no association between both maternal and paternal ages and vaccination status in this age group.
The relationship between childhood vaccination status and maternal/paternal ethnicity is also controversial [11,28,34,35]. The reasons for this phenomenon are complex and often location specific [11]. One study in Lao PDR showed that   Laolum, which was considered to be a dominant ethnic group, was better vaccinated than the other ethnic groups [28]. A qualitative literature review conducted in Lao PDR found that immunisation obstacles are rather linked to culture and ethnicity, as the health system tends to be tailored to the culture and predominance of ethno-medical beliefs among the ethnically dominant group [36].
Multivariate analysis showed the association between ethnicity of the mother and child vaccination status. Father's ethnicity was excluded from the final multivariate logistic regression model because of high multicollinearity.
Numerous studies have shown the association between failure to vaccinate or complete the vaccination schedule and maternal/paternal occupation or low socioeconomic status of the household, as maternal/paternal occupation is often considered to be a proxy for the level of income/socio-economic status of the household [8,9,10,11,12,13,17,22,23,36,37,38,39]. Maekawa et al. found no association between vaccination status and maternal/paternal occupation in Lao PDR [40]. This finding may be explained by the fact that the EPI programme in Lao PDR is free of charge; therefore, maternal/paternal occupation may not affect vaccination status. Alternatively, it can be explained by the possibility that outreach services can reduce socioeconomic differentials [18]. Final multivariate analysis of this study did not show any association between vaccination status and maternal/paternal occupation. However, Hossenpoor et al. reported a large difference in the national DTP3 immunisation coverage between the richest and The variables included in the model were "Maternal ethnicity", "Maternal/Paternal occupation", "Maternal/Paternal education", "Time taken to the nearest health facility", "Birth place", "Received vaccination at hospital", "Received vaccination during outreach activity", "Information of vaccination by vaccination card", Information of vaccination date by medical staff", and "Information of vaccination date by vaccination card". Backward stepwise selection was applied. "Paternal ethnicity" was dropped due to multicollinearity.
poorest quintiles in Lao PDR; hence, the within-country economic-related inequality should be investigated in future studies [10].
Many studies have shown that maternal education or literacy is positively associated with the vaccination status of children, such as complete and timely immunisation [1,5,6,12,13,18,19,28,38,40,41]. However, Parashar's study showed that a child's vaccination status is affected not only by maternal education level but also by education level of women in the wider context, at the community level [38]. Johri et al. suggest that improving health literacy may circumvent barriers due to low education level and improve vaccination coverage [24]. A study conducted in Lao PDR demonstrated that maternal education is associated with immunisation services attendance [39]. Three further studies in Lao PDR showed that maternal education or literacy is associated with vaccination status [28,36,40]. Fewer studies have measured and showed the significant association between paternal education and vaccination status [13,24,42,43]. In Lao PDR, one study found that low paternal education level was a risk factor of non-vaccination [39].
Bivariate analysis revealed that maternal/paternal education was associated with vaccination status. The association with paternal education was significant in the multivariate analysis.

Health system and health service utilisation factors
Access to the nearest health facilities is one of the well-known factors associated with vaccination status [6,8,23,28,34,39,40]. Three studies from Lao PDR demonstrated that distance to the health facility or the zone of residence is associated with vaccination status [28,39,40]. This study focused on time, rather than distance, to health facilities because access depends not only on distance but also on road accessibility and on the availability of transportation. Time taken to the nearest health facility was not significantly associated with vaccination status in the multivariate analysis.
Evidence shows an association between vaccination status and the location where caretakers or children receive health-care services [5,8,21]. Caretakers' experiences of health-care services and the information provided during the services may shape their attitude towards future use of health services, but this is context specific [9,21,23,25,28,39,43]. This study showed that facility-based delivery, that is, vaccination within a hospital or outreach setting, was associated with full vaccination of the children in the bivariate analysis. However, this association was not significant in the multivariate analysis.

Communication, information, and knowledge factors
A number of studies found that comprehensive and appropriate information provision and access to information affect vaccination status [3,6,36]. Several Article No~e00265 studies from Lao PDR showed that maternal knowledge of diseases targeted by immunisation programs and of immunisation age and schedules are associated with vaccination status [39,40,44]. The local authority such as chief of village is considered to be a key person to disseminate information regarding health in the village and our previous study in Lao PDR showed that notification of the vaccination date by the local authority increased the odds of children being fully vaccinated [30]. Nanthavong et al. reported that the absence of advice given at birth independently associated with non-vaccination of children [28]. This study showed that notification of vaccination date by medical staff increased the odds of full vaccination status and this finding may imply that the increased number of contacts between the caretakers and the medical staff.
Another study showed that use of appropriate information and communication strategies through the radio and TV increased vaccination coverage when the information or message were adapted to the local cultural health belief system or perspective, so that information was understandable and acceptable [6,36]. In Lao PDR, IEC materials related to immunisation such as posters are distributed to the health facilities by the Ministry of Health and the radio and TV are also used to disseminate information about vaccination campaigns. This study showed that a limited number of subjects made use of information provided through the radio, TV, or posters.
This study has several limitations. First, all the children and their caretakers who did not possess any certification of vaccination were excluded from this analysis.
Children and mothers with vaccination cards were compared with those without. The following factors were associated with "possession of vaccination cards": time taken to reach the nearest health facility, absence of traditional birth attendants at the time of birth, and vaccination within a hospital or health centre setting (data not shown). Second, only written records (vaccination cards and mother and child handbooks) were used in order to avoid inaccuracies in the vaccination history. Parent recollection of vaccination was not accepted. Vaccination cards and mother and child handbooks were the sole source of immunisation information in this study. Third, this study did not focus on immunisation system factors, except for access to and distance from vaccination services [8]. Factors such as the availability of health-care workers and equipment for vaccination, and the limited knowledge of health-care workers, resulting in missed opportunities to vaccinate, were not included [5,6,8,13]. Fourth, which information or knowledge is useful for caretakers is not clear, as this study did not investigate the information obtained by caretakers. Finally, this was a crosssectional study; therefore, a cause-and-effect relationship between childhood immunisation and risk factors was difficult to identify.
This study is the only nationwide study to identify factors associated with the vaccination status of children in Lao PDR, except for the Multiple Indicator Cluster Survey (MICS) data analysis and systematic review of qualitative data conducted by the Swiss Centre for International Health to investigate the association between gender and immunisation [36]. The MICS data analysis showed that maternal education and maternal tetanus toxoid status were strongly associated with child immunisation status, and the review of qualitative data indicated that sociodemographic factors, community awareness on immunisation, and quality of services were associated with vaccination status [36].

Conclusions
This study found that the proportion of infants who were fully immunised was still lower than the national target and maternal ethnicity, paternal education, and notification of the vaccination date by medical staff were associated with full vaccination status. It also found that TV, radio, and posters were underutilised sources of information on vaccination programs or of vaccination date notification. This finding suggests that targeted and culturally acceptable sub-group specific messages, using appropriate means of communication, are necessary [39]. It also suggests that fathers may play a role in decision-making as well and that the vaccination status may be improved by providing health education to improve health literacy of both mothers and fathers [24,39]. This study highlights that health-care workers should clearly provide information on vaccinations, including the vaccination schedule.
The completion of the recommended vaccine schedule is determined by numerous factors, and some of these are location specific. Identification of these factors should result in actions facilitating the optimal use of vaccination services by all the children in Lao PDR.

Declarations
Author contribution statement Tomomi Kitamura and Anonh Xeuatvongsa: Conceived and designed the experiments; Analyzed and interpreted the data; Wrote the paper.
Masahiko Hachiya: Conceived and designed the experiments; Wrote the paper.
Shinsuke Miyano: Conceived and designed the experiments.
Tetsuya Mizoue: Analyzed and interpreted the data; Wrote the paper.

Funding statement
This work was supported by The Grant for National Center for Global Health and Medicine .