Trends and Determinants of Full Immunisation among Children Aged 12–23 Months: Analysis of Pooled Data from Mozambican Household Surveys between 1997 and 2015

The 1974 Expanded Program on Immunisation has saved millions of children worldwide by promoting full immunisation coverage (FIC). However, forty years later, many sub-Saharan African countries remain well below its target of 90% FIC. This study analysed the level, trends and determinants of FIC in 4322 Mozambican children aged 12–23 months from pooled data from four national surveys between 1997 and 2015. Descriptive statistics and multivariable logistic regression models were performed to analyse the factors associated with full immunisation coverage. Overall, the coverage of fully immunised children increased from 47.9% in 1997 to 66.5% in 2015, corresponding to a 1.8% yearly increase. The needed FIC growth rate post-2015 was 4.3 times higher. Increased maternal education and a higher household wealth index were associated with higher odds of FIS. Furthermore, attending antenatal care (ANC) visits, institutional delivery and living in southern provinces were also associated with increased odds of FIS. Between 1997 and 2015, FIC among 12–23-month-old children made modest annual gains but remained well below international targets. Factors related to access to healthcare, educational level, socioeconomic status and geographical location were associated with improved FIC. Targeted interventions to expand these factors will improve immunisation coverage among Mozambican children.


Introduction
In 2015, the United Nations General Assembly established the Sustainable Development Goals (SDGs) under the slogan "leave no one behind." The third SDG is to ensure healthy lives and promote well-being for all ages [1]. Child immunisation is one of the most cost-effective and sustainable strategies to prevent morbidity and mortality and to ensure health and well-being across the lifespan, especially among children living in low-income countries such as Mozambique [1].
Immunisation coverage is the proportion of a population vaccinated with the basic schedule during a certain period in a geographic area. It is an important indicator of the World Health Organization's (WHO) 1974 Expanded Program on Immunisation (EPI), which aims to provide vaccines against preventable diseases to all children at risk [2,3]. Specifically, full immunisation coverage (FIC) is defined as the proportion of children who have received one dose of Bacillus Calmette-Guérin (BCG), three doses of poliomyelitis (OPV), three doses of the combined diphtheria, tetanus toxoid and pertussis (DTP or other polyvalent vaccines including DTP) and one dose of measles (either monovalent or as measles-containing vaccine combinations) between the ages of 12-23 months [4,5]. The Global Vaccine Action Plan (GVAP), a joint plan developed by UNICEF and WHO, recommends that all countries reach 90% vaccination coverage for all essential vaccines. Global FIC has increased in the last decades, contributing significantly to a reduction in morbidity and mortality from vaccine-preventable diseases [6]. For instance, from 2000 to 2016, immunisation coverage of the third dose of the DTP vaccine (DTP3) increased from 72% to 86% globally, the result of a combination of several national and international efforts [7]. However, FIC remains lower in sub-Saharan Africa (SSA), where it varies from 31-76%, far from GVAP target of at least 90% global FIC by 2020 and at least 80% FIC in every district for all vaccines in the national immunisation programme [8].
The EPI in Mozambique was established in 1979, with the ultimate goal of reducing child morbidity and mortality by vaccine-preventable diseases through immunisation services [3]. Mozambique's child immunisation programme is provided free of charge through primary health care delivery including health facilities, mobile teams and community health workers [3]. Household surveys conducted in the country show that between 1997 and 2015, national DTP3 coverage improved from 58% to 82%, and BCG coverage reached 90% [3,9]. However, although the FIC of children aged 12-23 months increased from 47% in 1997 to 64% in 2011, by 2015, it had plateaued at 66% [9,10]. Therefore, with this declining rate, Mozambique likely did not reach the GVAP target in 2020.
In addition, Mozambique experiences substantial geographical differences in FIC, ranging from 50% in the central region to 87% in the southern region [9]. Studies conducted in different SSA countries have identified several determinants and health system factors requisite for reaching FIC. These include: institutional delivery [11][12][13]; increased maternal education [11][12][13]; residing in urban areas [11]; antenatal care (ANC) attendance [11,13]; and increased household wealth [14]. Despite the correlation between these factors and FIC, few studies have assessed the factors related to complete immunisation status in Mozambique. Those that did are restricted to the district level, leaving a large knowledge gap at the national level [15,16]. Three Demographic and Health Surveys (DHS, 1997(DHS, , 2003 and 2011) and the 2015 Malaria, HIV/AIDS, and Immunisation Indicator Survey (IMASIDA) were conducted across the country between 1997 and 2015, and these provide an opportunity to measure and describe FIC and its associated determinants at the national level. The objective of this study was to analyse trends and factors associated with full immunization status among Mozambican children aged 12 to 23 months old between 1997 and 2015.

Study Design and Data Sources
In this study, we analysed a pooled dataset from multiple national representative cross-sectional household surveys (DHS 1997, DHS 2003and DHS 2011, and IMASIDA 2015 [9,10,17,18]. The surveys were designed to collect characteristics of the household, including maternal and child health status, through a country-wide multistage and stratified random sample. Survey information was obtained through questionnaires administered to women who were between 15 and 49 years of age who provided information on the household's sociodemographic, economic and health status, including maternal and child health, environment, behaviour, and pre-and postnatal care. The survey response rate of the interviewed women was high overall at 91.5%, 90.9%, 98.9% and 94.5% in 1997, 2003, 2011 and 2015, respectively. Data collection was conducted between March and June, August and December, April and November, and June and September for DHS 1997, DHS 2003, DHS 2011 and IMASIDA 2015 surveys, respectively. Detailed methodology for the survey's participant selection has been described elsewhere [9,10,17,18]. Permission to use these datasets was granted by the Monitoring and Evaluation to Assess and Use Results Demographic and Health Survey (MEASURE-DHS).

Study Setting
Mozambique is a southern East African country covering 801,590 km 2 (Figure 1). Its estimated 30,066,648 inhabitants reside primarily (65.9%) in rural areas and about 15.3% of the population are children below the age 5 years of which 17.3% are children living the second year of life (Table S1 and Figure S1) [19]. Following independence from Portuguese colonial rule in 1975, Mozambique's 16-year civil war destroyed its infrastructure and displaced more than half of its population [20]. Presently, the country is classified as a low-income country (LIC) by the World Bank, with a gross domestic product per capita (average annual income) of USD 503 in 2019 [21]. According to the United Nations 2020 Human Development Index, Mozambique was ranked 181 out of 189 countries, decreasing by one point from its ranking in 2019 and 2018 [22]. The 1979 EPI launch in Mozambique introduced BCG, polio, DTP and measles vaccines to the population [3]. Gradually, more vaccines were added to the national schedule, including an updated DTP (containing additional immunogens for hepatitis B and haemophilus influenzae type B) in 2008 and pneumococcal conjugate vaccine (PCV) in 2013. Rotavirus vaccine (RV), injected polio vaccine (IPV) and the second measles dose were introduced in 2015, data from which were not captured in the 2015 survey. The measles and rubella vaccine (MRV) was introduced in 2019 [3]. Despite increased availability of these vaccines, vaccine coverage, accessibility and uptake has remained below EPI targets.

Survey Eligibility Criteria
The present analysis included women surveyed who had a living child aged 12-23 months at the time of the survey. Interviewers communicated with study participants using participants' preferred language. When available, children's health cards, which contain information on vaccination doses and related dates, were used to determine children's immunisation status. When health cards were not available, mothers' verbal reports by recall of the vaccines their children had received were used to determine children's immunization status. Table 1 details when health cards and when mothers' verbal reports were used across surveys. For this analysis, full immunisation status is the outcome variable of interest. The WHO guideline considers a fully immunised child to have been administered eight doses in total: one dose of BCG; at least three doses of OPV (excluding that given immediately after birth); three doses of DTP; and one dose of measles vaccine between 12 and 23 months of age [23]. This outcome variable aligns with similar studies across many SSA countries [13,[24][25][26][27]. Each vaccine dose variable had five response categories: (0) no vaccine; (1) vaccination dates on card; (2) reported by mother; (3) vaccination marked on card; and (8) don't know. The categories (1), (2) and (3) were recoded as "1" to indicate those that received vaccines and (0) and (8) were recorded as "0" to indicate that no vaccination was received. The vaccination status of each of the 8 doses were then combined to compute a final variable, "immunisation status," categorised as "1" for fully immunised and "0" for not fully immunised, capturing children who had missed one or more of the 8 doses.

Factors Associated with Full Immunization Status
Drawn from the literature and data availability across all surveys, a total of 13 variables were selected for potential association with Mozambican children achieving full immunisation status. The variables included in this analysis were: (1) maternal age at the date of the survey, grouped as 15-24, 25-34 and ≥35 years old; (2) maternal educational level defined as illiterate, primary and secondary or above; (3) marital status, which originally had six categories (single, married, living with a partner, separated, divorced, widowed) and which was recoded into three categories (single/never in a union, married/living with a partner and divorced/separated/widowed); (4) mother's occupation defined as unemployed (not working/household domestic) and employed (professional, clerical, sales, skilled and unskilled manual, services, agriculture, self-employed and all others); (5) geographic location whereby the provinces were included separately and aggregated to reflect the three regions (northern, central and southern) of the country; (6) area of residence, categorised as urban and rural; (7) wealth index, which was maintained as defined in each survey: poorest, poor, middle, richer and richest; (8) religion, the categorization of which varied among surveys but was regrouped to reflect four standardised responses to all datasets: Catholic, Islamic, Protestant and others, which also included no religion (although religion was analysed in all surveys, this variable was not included in the multivariable regression model due to its possible collinearity); (9) number of ANC visits (no visits, 1 to 3, ≥4); (10) place of delivery (at home/other, at health facility); (11) sex of the child (male and female); (12) birth order (1, 2 to 3, ≥4); and (13) health card possession (seen, not seen, no card).

Statistical Analysis
Descriptive statistics were used to summarise the selected factors. The FIC and its 95% confidence interval (95CI) were computed for each survey per each potential determinant. Then, per determinant we estimated the annual exponential growth rate (AGR) of FIC, which is a relative yearly growth rate between two subsequent surveys, s and s*, using the formula: annual.growth.rate s to s * = e log(Covs * )−log(Covs) years * −years where Cov s and Cov s* represent coverages of two subsequent surveys, respectively, and year s and year s* are the years of the two subsequent surveys, respectively. The standard error for AGR was computed through the delta method, from which 95CI were produced. In addition to the AGR, we computed the needed annual growth rate (NAGR) to reach 90% FIC by 2020 since 2015. To improve readability, we present the AGR and the NAGR in percentages by subtracting 1 and multiplying by 100, abbreviated AGRp and NAGRp, respectively.
To analyse factors associated with full immunisation status, we used a mixed-effects logistic regression with the primary sampling unit (PSU) as random intercepts. This analysis assesses the pooled association across the period of time between 1997 and 2015. All covariates included in the model are based on the literature review and data availability. In addition, a linear term of the year of the survey was introduced in the model to capture potential changes over time. A linear term was chosen to improve the interpretability of the parameters. The province and the urban/rural variables were included as covariates in the models. The province is included as dummy indicators coded as sum contrasts. Therefore, its coefficients are to be interpreted as deviations from the overall country average. In addition, complex sampling logistic regression (reported in the Supplementary Materials) specific to each survey was performed as a sensitivity analysis for the overall analysis. We report the odds ratio (OR), 95CI and the p-values. Data management procedures and descriptive and complex survey analysis were conducted using Statistical Package for the Social Sciences (SPSS) version 26.0 [28]. The mixed-effects model was performed in R version 4.0.3 (R Foundation for Statistical Computing, Vienna, Austria) using maximum likelihood estimation with 30 Adaptive Gaussian Quadrature's through the package GLMMadaptative [29].

Sociodemographic and Economic Characteristics of the Mothers and Children
We included data of 1240 (1997), 1931 (2003), 2325 (2011) and 1131 (2015) children aged 12-23 months. Across all surveys, the majority of mothers surveyed were between 25 and 34 years of age, had only obtained a primary school education level, were married or living with a partner, and belonged to the poorer or poorest wealth index. Although maternal employment decreased by 18.7% between 1997 and 2015, improvements were observed in ANC visits, which increased from 48.7% to 57.3%, and in institutional delivery, which increased from 48.9% to 72.1% between 1997 and 2015 (Table 1).

Full Immunisation Coverage Rate and Trends among Children
The prevalence of fully immunised children was 47 9 to 71.2%) in 2011. In 2015, however, the highest coverage (67.1%) was observed among children from mothers 25-34 years old (95% CI: 60.9 to 72.7%). Across all surveys, FIC was higher in children whose mothers had completed secondary school or above, were single or had never been in a union, lived in urban areas and in the southern region of the country, belonged to the highest household wealth index, attended four or more ANC visits and had institutional delivery. The child's gender did not present significant differences across all surveys. Regarding birth order, FIC was higher among firstborn children in the 1997 to 2011 surveys. However, in 2015 the coverage was higher for second-and thirdborn children. In all surveys, possession of a health card was related to higher rates of FIC (Table 2).

Factors Related to Full Immunisation Status
The crude odds ratio and baseline descriptive statistics of each survey are shown in Supplementary Tables S1-S4 for the 1997, 2003, 2011 and 2015 surveys, respectively. A total of 4322 children aged 12-23 months were included in the pooled multivariable analysis, which showed that maternal education, household wealth index, religion, ANC visits, place of delivery, birth order and geographic area were factors associated with children's full immunisation status as presented in model 1 (Table 4).   Compared to children whose mothers had no formal education, children born to mothers who attained primary and secondary or above were 1.41 times (AOR = 1.41, 95% CI: 1.19 to 1.68) and 1.70 times, (AOR = 1.70, 95% CI: 1.24 to 2.34), respectively, more likely to achieve full immunisation status. Regarding household wealth index, children from households in the middle, richer and richest quintiles had 1.47 times (AOR = 1.47, 95% CI: 1.16-1.86), 1.43 times (AOR = 1.43, 95% CI: 1.10 to 1.87) and 1.47 times, (AOR = 1.47, 95% CI: 1.04 to 2.10), respectively, higher odds of becoming fully immunised compared to children from the poorest quintile households. Compared to children whose mothers identified as Catholic, children whose mothers identified with other religions were 24% (AOR = 0.76, 95% CI: 0.59 to 0.96) less likely to achieve complete immunisation. Children whose mothers attended 1 to 3 and ≥4 ANC visits had 4.16 (AOR = 4.16, 95% CI: 3.09 to 5.61) and 4.86 (AOR = 4.86, 95% CI: 3.61 to 6.54) higher odds, respectively, of achieving complete immunisation status compared to children whose mothers had not attended ANC visits. The analysis also showed that children whose mothers delivered in health facilities were 1.68 (AOR = 1.68, 95% CI: 1.42 to 1.98) times more likely to be completely immunised compared to those whose mothers delivered at home or elsewhere. Compared to firstborn children, the odds of being fully immunised decreased by 28% (AOR = 0.72, 95% CI: 0.55 to 0.94) among fourthborn children. Among provinces, compared to Maputo City, children from Maputo Province had 1.77 (AOR = 1.77, 95% CI: 1.10 to 2.86) times higher odds of completing the full immunisation schedule. Children from Sofala had similar (AOR = 1.00. 95% CI: 0.65 to 1.56) chances as children in Maputo City. Children from the provinces of Manica, Zambézia and Nampula were 44% (AOR = 0.56, 95% CI: 0.37-0.87), 55% (AOR = 0.45, 95% CI: 0.28 to 0.71) and 53% (AOR = 0.47, 95% CI: 0.30 to 0.76) less likely, respectively, to be fully immunised than those in Maputo City.

Discussion
This study assessed the level and trend of FIC and associated factors among children  [30][31][32][33][34][35][36][37][38][39][40]. These differences can be attributed to the sociocultural and political environments, and the health services' performance and coverage [13,41]. The present study's multilevel analysis showed that many factors related to the mother are directly associated with the child's immunisation status outcome, particularly maternal education level. The household wealth index was also significantly associated with FIC. These results are aligned with studies conducted in other developing countries, such as Senegal [13], Ethiopia [27,42] and Papua New Guinea [14], and in several East African countries [43]. Some studies have hypothesised that mothers who are well-positioned economically are more likely to understand public health messages such as those related to the uptake of child immunisation services [41]. Moreover, other studies have shown that mothers who are socially at an advantage are exposed to environments that may help them to capture important health information [14,44]. Data from Mozambique's 2017 population census estimated that the national illiteracy rate attenuated from 50.4% in 2007 to 39% in 2017. Concerningly, differences between gender demonstrate that almost half of all adult women (49.4%) are illiterate compared to men's 27.2% illiteracy rate. Geographic location is also important; between rural and urban environments, 62.4% of rural women were found to be illiterate, compared to only 25.7% of urban women [45].
In the present study, mothers who profess to following religions other than Catholicism were associated with the lowest odds of having a child fully immunised compared to mothers professing Catholicism. This was also observed in Ghana's 1998 to 2014 pooled DHS data, which showed that compared to children whose mothers professed Christian religions, children whose mothers professed traditional religions or who had no religion had 40% and 42% lower odds of achieving complete immunisation status, respectively [46]. Moreover, a multi-country study conducted in SSA found that in 9 out of 15 (60%) countries, FIC was associated with children with Christian mothers, while children whose mothers prescribed to folk religions had a lower probability of achieving complete immunisation [5]. Additionally, in our study, the 2015 survey showed that children whose mothers identified as Islamic had 2.62 times higher odds (Table S8) of achieving complete vaccination when compared to children whose mothers were Catholic. This has previously been observed in Mozambique and also in Liberia, where the FIC was higher among children whose mothers identified as Muslim [5]. Mozambique's last national census reported a slight increase in people who identify as Muslim, from 17.9% in 2007 to 18.9% in 2017, while the number of those identifying as Catholic decreased from 28.4% to 27.2%, respectively [45]. However, in the present study, the Christian religion is disaggregated into Catholic and other Protestants, unlike other studies here discussed.
Our results indicate that children born to mothers who attended one or more ANC visits were more likely to be fully immunised compared to children whose mothers did not. Similar associations with ANC visits and FIC were seen in other low to middle income (LMIC) SSA countries, including Mozambique [13,27,42,43,47,48]. According to a national assessment of 1643 Mozambican health facilities in 2018, 92% of them provided prenatal care and 90% provided routine child immunisation services. This may explain the association found between ANC visit attendance and FIC and support the idea that when mothers access prenatal care or clinics in general, they are more likely to be exposed to and uptake immunisation services [49]. Mozambique's national health education efforts, including health weeks and the Reach Every District program, which aims to bring maternal and child health services directly to communities, may have also contributed to improved FIC by increasing the quantity of and access to ANC services [3,13,16]. Additionally, other studies show that mothers who attend ANC visits [42] are advised by health professionals to adhere to the recommended prenatal and child immunisation schedule [27], confirming that for mothers who attend ANC, decisions about vaccination begin long before delivery [50].
In the present analysis, children whose mothers delivered in health facilities were 1.68 times more likely to achieve complete immunisation. Similar results were also reported in Senegal and Ethiopia, with 1.67 and 2.10 times higher odds, respectively [13,48]. In contrast, in Nigeria, children whose mothers delivered in a health facility were found to be 38% less likely to obtain full immunisation [51]. Interestingly, this contradicts findings in other regions of the world. For example, in Myanmar, children whose mothers delivered at home were more likely to achieve full immunisation [47]. With respect to birth order, our results show that children born after the firstborn (higher birth order) experience a decrease in the probability of becoming fully immunised. This aligns with birth order and FIC results in Cameroon, Nigeria, Papua New Guinea and the Sinana District in southeast Ethiopia [14,42,51,52]. Various explanations have been raised to account for this phenomenon since it is sometimes presumed that increased maternal experience would lead to better health outcomes among children born later. Those studies suggest that children higher in the birth order may compete for resources as the household conditions may have changed compared to when older siblings were born, [52,53] leading to decreased parental ability to fulfill immunisation services for subsequent children [51].
The present study has raised important geographical differences, with full immunisation status found to be associated with children from southern provinces compared to the central and northern provinces. This aligns with two prior studies conducted at the district level. In Magude district, a southern province of Maputo, FIC was found to be 71.8% [48], while in the rural districts of Gurué and Milange, in the central province of Zambézia, FIC was much lower at 49.7% and 48.0%, respectively [16]. Although the number of health facilities has increased in Zambézia and Nampula, the ratio of maternal and child health (MCH) nurses to the population remains low [54]. In addition, these provinces' high populations, low number of health care workers per capita and inadequate health infrastructure could contribute to their low FIC observed. Moreover, the long distances travelled by the population to the health facility, access to transportation and the dispersion of communities vary across these provinces [3]. These findings highlight the need for greater investment of the EPI in reaching the most vulnerable, regardless of the area of residence. Studies conducted elsewhere have also reported an association between geographic location and children's immunisation status. These studies attributed this difference to the cultural beliefs of diverse patient populations, the low quality of services provided by health professionals in these areas [13] and logistical challenges such as inadequate vaccine storage cold chains [13,42]. In India, an association between geographic variation and negative health outcomes, including low FIC, has been attributed to a high poverty level in some areas, parental preferences for male children, low maternal education levels and a lack of maternal autonomy [13,55].
There are a few limitations in the present study. First, the analysis of the factors associated with FIC lacks factors not related to the mother and the household such as, for example, political and governance issues, due to data unavailability. Some of these are captured in the random-effects included in the analysis. Second, a proportion of the data used in this study's analysis may be affected by recall bias. As noted, immunisation status of children without health cards was obtained through their mother's verbal reports, which may be inaccurate. Although the fraction of children without a health card decreased substantially between 1997 and 2015 (from 19.7% to 8.0%, respectively), the children with unseen cards increased slightly (from 13.9% in 1997 to 17.5% in 2015) over the period of the study. Depending on the accuracy of the mothers' recollections of their children's vaccination history, the overall FIC could change.

Conclusions
The household survey analysis from 1997 to 2015 showed that in Mozambique, full immunisation coverage among children remains below WHO and UNICEF targets. Although the differential coverage per each factor studied did reduce over time, factors such as the maternal education level, household wealth index, ANC attendance, institutional delivery, birth order and geographic location were associated with achieving full immunisation among 12-23-month-old children. Attention to these factors in public health programming will likely help reduce coverage gaps within Mozambique.
Supplementary Materials: The following supporting information can be downloaded at: https: //www.mdpi.com/article/10.3390/ijerph20032558/s1, Table S1: Projected Mozambique Population for 2020 (based on Census 2017) per province, Table S2: Descriptive and bivariate regression analysis of children aged 12-23 months, 1997 survey, Table S3: Descriptive and bivariate regression analysis of children aged 12-23 months, 2003 survey, Table S4: Descriptive and bivariate logistic regression analysis of children aged 12-23 months, 2011 survey, Table S5: Descriptive and bivariate regression analysis of children aged 12-23 months, 2015 survey, Table S6: Tests for interaction terms between each variable and time, Table S7: Mixed-effect logistic regression of fully immunised children with linear time interactions, 1997-2015, Table S8: Multivariable logistic regression of full immunised children aged 12-23 months in 1997 to 2015 surveys. Figure S1: Population pyramids of Mozambique and its provinces, using Census 2017 projections for the year 2020.  Institutional Review Board Statement: Ethical review and approval were waived for this study due to public availability of the data for analysis. Ethical approval was granted by the National Bioethics Committee for Health (CNBS) and written informed consent made available for the 2011 and 2015 surveys.
Informed Consent Statement: Informed consent was obtained from all subjects involved in surveys. However, in the 1997 and 2003 surveys, guardians consented verbally to children's participation. The study used publicly available data through request to the MEASURE-DHS program website. The confidentiality and anonymity were maintained in all surveys. Data Availability Statement: Datasets and materials are available in the DHS program website and were granted after the purpose and objectives of the study were declared. Administrative permissions to access raw data was not required.