Vaccination timeliness and associated factors among children aged 12-23 months in northwest Ethiopia: community-based study

Background: vaccines are the most effective preventive and success of public health to control and eradicate serious childhood diseases. Timely childhood vaccination can help for children to develop antibody against vaccine preventable diseases. Evidences on childhood vaccination timeliness, however, there are limited in developing countries including Ethiopia. Therefore, this study was aimed at assessing vaccination timeliness and associated factors among children aged 12 to 23 months in Jabitehnan district, northwest Ethiopia. Methods: A community based cross-sectional study was conducted in Jabitehnan district from February to March 2020. A total of 548 children aged 12-23 months were included using multi-stage and simple random sampling technique. Binary logistic regression model was tted to identify factors associated with vaccination timeliness. Adjusted odd ratio (AOR) with 95% CI and p-value less than 0.05 were used to declare statistically signicant variables. Results: A total of 13.1% (95 % CI: 10.1-15.8) of children were received childhood vaccines in the recommended time interval. Higher level of maternal education (AOR: 2.73; 95% CI: 1.14-6.50), history of abortion (AOR: 3.45; 95%CI: 1.54-7.74), knowledge (AOR: 1.79; 95%CI: 1.10-3.18) and favorable attitude (AOR: 3.38; 95%CI: 1.83-6.24) were positively associated with vaccination timeliness. While home delivery (AOR: O.35; 95%CI: 0.18-0.68) and rural residence (AOR: 0.31; 95%CI: 0.14-0.65) were negatively associated. Conclusion: The overall childhood vaccination status was low in the study area. Children were received the rst dose than the other doses/vaccines. BCG later time abortion, incorporate vaccination timeliness in the childhood vaccination plan, and better to monitor and evaluate as one potential indicator to enhance the immune status of children. Health planners and managers should also improve women’s awareness to enhance their attitude towards childhood vaccination. Furthermore, it is better to promote institutional delivery service utilization to enhance childhood vaccination timeliness.


Introduction
Immunization is the process by which a person is made immune or resistant to an infectious disease, typically by the administration of a vaccine (1). The Expanded Program on Immunization (EPI) was started in early 1974 to give all basic vaccines and immunize every child around the world and launched in Ethiopia since1980 (2). Immunization is a central pillar of universal health coverage (3), and one of the most effective and successful means of public health interventions to control and eradicate serious diseases (4). It is a highly effective strategy that helps the parents to prevent their children from major infectious diseases, sequelae, hospitalization and even death (5).
World Health Organization (WHO) recommends that vaccines must be administrated during the rst year of life within a speci ed schedule and time range (6). Immunization timeliness is de ned as the administration of vaccines at the earliest appropriate age and recommended intervals between vaccine doses (7). Vaccinating children at an appropriate time interval is an important mechanism to protect diseases adequately since early vaccination can result in failure to generate a protective antibody against the diseases and delayed vaccination end up with risk factors for vaccine preventable diseases (8,9).
Increased compliance to vaccine timeliness safeguards that children are protected prior to exposure and controls morbidity through improving population immunity and potential spread of communicable diseases, particularly in the form of disease outbreaks (10,11).
About 86% of the children receive vaccines and prevents 2-3 million deaths every year from childhood vaccine preventable diseases in the world (12). Despite this success of childhood interventions approximately 1.5 million children died by vaccine preventable diseases each year, particularly in developing countries (13). Low and middle income countries (LMICs) encountered a disproportionately high burden of vaccine-preventable diseases (14). Every year more than 6.3 million children in low-and middle-income countries die before they reach their fth birthdays and the leading cause of this is ineffectiveness of vaccine administration (15). In sub-Saharan African countries, vaccine preventable diseases (VPDs) are also the major contributors to high child mortality (16).
In Ethiopia, under one mortality is 40 per 1000 live births per year and the leading cause of this death is vaccine preventable diseases (17). Moreover, about 7,951 suspected measles cases and around 3.5 million children become susceptible to measles every year in the country (18).
Although childhood vaccination coverage in Ethiopia has shown improvements (more than 90%) except measles (83%), childhood vaccine preventable disease outbreaks and high associated childhood mortality rate are still common nationwide. It was mainly because of the failure to achieve 'herdimmunity' (18). This indicates that maximizing vaccination timeliness to attain the full bene ts of vaccinations is crucial and untimely vaccination coverage may mask the absolute timely vaccination coverage (19).
Childhood vaccination timeliness is low in many African countries, including Ethiopia ranged from 6.2-68% (20)(21)(22). Both early and delayed childhood vaccination have their own disadvantages i.e. early vaccination can result in failure to generate a protective antibody against the diseases while delayed vaccination end up with risk factors for vaccine preventable diseases (8,9).
The high childhood mortality rate due to vaccine preventable diseases indicates that being satis ed with vaccination coverage alone can mislead to false assumption for vaccine preventable disease protection. Studies revealed that a timely childhood vaccination is a good quality indicator for the expanded program on immunization to protect children from vaccine preventable diseases through enhancing seroconversion rate of vaccines.
However, there are limited studies in our country on childhood vaccination timeliness. Therefore, this study was aimed at assessing vaccination timeliness and associated factors among children aged 12 to 23 months in Jabitehnan district, northwest Ethiopia.

Study design and settings
A community based cross-sectional study design was conducted among mothers/caregivers of children aged 12 to 23 months at Jabitehnan district, northwest Ethiopia. The study was done from February to March 2020. Jabitehnan is located 180 Km in the southwest of Bahir Dar (Capital city of Amhara National Regional State) and 387 Km in the northwest of Addis Ababa (Capital city of Ethiopia  (24). The district has thirty-nine rural and three urban kebeles. On top of that, there are eleven health centers and 41 health posts in the district. All of these health facilities provide both outreach and static childhood vaccination services.

Population and sampling procedures
The source and study population were all children aged 12 to 23 months who had started vaccination and vaccination card or registered in childhood vaccination register in Jabitehnan district and selected kebeles of the district, respectively. All mothers /care givers of children aged 12 to 23 months who had started vaccination and who had a vaccination card or a vaccination register in the selected kebele were included in this study, however, those who were severely ill during data collection and children who had vaccination cards but no registration date of vaccination or date of birth either in the card or in the infant immunization register were excluded from the study.
The sample size was determined using the single population proportion formula by assuming a 6.2% proportion of children received timely vaccination study in northeast Ethiopia (22), 3% margin of error, 95% con dence level, 10 % non-response rate and 2 design effect. The nal sample size was 548.
A multi-stage simple random sampling technique was used to select study participants. First the kebeles of the district were strati ed to 39 rural and 03 urban. From the total of 42 kebeles in the district ten (one urban and nine rural) were selected randomly using the list of all eligible children aged 12 to 23 months from the family folder and infant immunization registers of the selected health posts. Health extension workers update the information recorded in the family folder at least once per month in every health posts. The list of all eligible children obtained from the health posts family folder were cross-checked with the infant immunization registers in the health posts and health centers to con rm the missing of eligible children from the sampling frame. The complete list of all eligible children in the selected kebele containing information about the name of a child, his/her parent's full name, household's unique identi cation number and sub-kebele/gotte/ was prepared by using family folders and infant immunization registers of the health posts and health centers. Proportional allocation of the sample was made to determine the required sample size from each selected kebele. Finally, simple random sampling technique was employed to select the required number of children from each selected kebele using the listed children as a sampling frame. The mothers/care givers of the index children were identi ed using the unique ID of the household in the selected kebeles.

Variables and measurement
Vaccination timeliness was the dependent variable, while socio-demographic related factors, such as age, sex of child, income, occupation, marital status, educational status of parents, residence, religion of parents, household size and birth order; access related factors: distance from vaccination site, mode of transportation, season of birth, availability of phone, availability of electronic media and place of vaccination; obstetric related factors: ANC visit, PNC visit, maternal conference participation, TT vaccination, pregnancy status, institutional delivery, birth attendance and parity; maternal awareness related factors: knowledge about vaccination and attitude towards vaccination were the independent variables. Timely vaccination: a child is considered to be timely vaccinated, If the child received BCG within the rst fty-six days, OPV1, penta1, PCV1 and Rota1 from 39 to 70 days, OPV 2, penta2, PCV2 and Rota 2 from 67 to 98 days, OPV3, penta3 and PCV3 from 95 to 126 days and measles vaccine 270 to 301 days of age of the child (6,22). On the other hand, the child was considered as early vaccinated when the child received at least one dose of the vaccine below the minimum recommended age for each antigens, and considered as delayed vaccination when the child received at least one dose of the vaccine above the maximum recommended age (6,22).
Good knowledge: Twelve knowledge assessment item questions each containing (0=no and 1=yes) alternatives were used and those who scored greater than 50 % of the total knowledge measuring score was considered as having good knowledge (25).
Favorable attitude: Eight Likert scale attitude assessment item questions each containing (1=strongly disagree, 2=disagree, 3=neutral, 4=agree and 5= strongly agree) alternatives were used and those who scored 75% or more the attitude measuring score were considered as having favorable attitude (22,26).

Data collection tools and procedures
The data were collected using interviewer administered semi-structured questionnaire. Five data collectors (nurses) and two supervisors (Health o cers) were used for data collection. The questionnaire had socio-demographic, awareness, obstetric characteristics of mothers, and access related factors parts.
The questionnaire was prepared rst in English and translated to Amharic and then back to English to maintain consistency. One day training was given for both data collectors and supervisors on the basic techniques of the data collection procedures. Pre-test was conducted at Dembecha district among 28 (5%) mothers/caregivers of children aged 12 to 23 months who had started vaccination and had a vaccination card or a list in the infant immunization register, and necessary modi cation was made based on the pre-test ndings. Completeness and consistency of the data were checked on the spot and daily basis by the supervisors and the principal investigator.

Data processing and analysis
The data were entered, cleaned and coded using Epi data software version 4.6 and exported to Statistical Packages for Social Sciences (SPSS) (version 22.0 Software for analysis. Descriptive statistics, such as mean, median, frequency and percentage were presented using texts, graphs and tables. Binary logistic regression model was used to identify factors associated with childhood vaccination timeliness. Those independent variables with p-value less than 0.2 during bi-variable analysis were taken into multivariable logistic regression analysis (22). Adjusted odd ratio (AOR) with 95% con dence level (95%CI) and p-value less than 0.05 during multivariable logistic regression were used to declare statistically signi cant association with childhood vaccination timeliness and the strength of association.

Results
Socio-demographic characteristics of participants A total of 543 mothers/caregivers of children aged 12 to 23 months interviewed with response rate of 99%. Nearly ninety percent (98.7%) of the participants were mothers of children and the remaining 1.7% of the respondents were caregivers. The mean age of the mothers/caregivers was 29.5 years (± 5.96SD) which ranges from 18 -50 years. Three hundred ninety (71.8%) of the respondents were in the age group of 25 -34 years. Nearly 90% of the participants were rural residents and over 95% of the respondents were Orthodox Christians. Two-third of the participants were farmers, more than 90% were married and threefth (60%) of the participants were unable to read and write. The mean ages of the children were 18.11months (±3.25SD) ( Table 1). Obstetric history, access to information and maternal awareness Over sixty percent (61.5%) of mothers/caregivers were attended institutional delivery and 76.6% received PNC services for their recent child. More than one-third (35.4%) of women had 5 or more parity and 56% of respondents did not participate in maternal conference. Almost half (48.3%) of mothers/caregivers had good knowledge and 47.3% mothers/caregivers had favorable attitude towards childhood vaccination. Sixty-nine percent of mothers/care givers had got information about childhood vaccination from health professionals ( Table 2).

Factors associated with childhood vaccination timeliness
The multivariable logistic regression analysis illustrates that variables such as maternal level of education, residence, history of abortion, place of delivery, knowledge and attitude of mothers towards vaccination were remained to be signi cantly associated with childhood vaccination timeliness among children aged 12 to 23 months in the study area.
Accordingly, children lived in rural areas were 69% (AOR: 0.31: 95% CI: 0.14-0.65) less likely to receive vaccines at the recommended age than urban children. Mothers/caregivers who gave birth at home were 65% (AOR: 0.35; 95%CI: 0.18-0.68) less likely to be vaccinated timely compared with those who gave birth at health facilities. Children of educated mothers were 2.73 times (AOR: 2.73; 95% CI: 1.14-6.50) more likely to receive childhood vaccination timely than mothers who can't read and write. Children of mothers who had history of abortion were 3.45 times (AOR: 3.45; 95%CI:1.54-7.74) more likely to receive vaccination timely compared with their counterparts. Children of mothers/caregivers with favorable attitude towards childhood vaccination were 3.38 times (AOR: 3.38; 95%CI: 1.83-6.24) more likely to be vaccinated timely than children of mothers with unfavorable attitude. Children of mothers/caregivers with good knowledge about childhood vaccination were 1.79 times (AOR: 1.79; 95%CI: 1.10-3.18) more likely to receive vaccination within the recommended time interval than their counterparts (Table 4).

Discussion
Vaccines are the most effective preventive, public health successful means of controlling and eradicating serious diseases (4). Vaccines are more effective when given with recommended time interval; since early vaccination can result in failure to generate a protective antibody against the diseases and delayed vaccination leads to more exposure to the diseases (8,9).
The overall childhood vaccination timeliness among children aged 12 to 23 months in Jabitehnan district were 13.1 % (95%CI: 10. 1-15.8). This implies that the remaining 76.9% children were susceptible for vaccine preventable diseases; since failure to be vaccinated on time would increase the susceptibility period of children through limiting the herd immunity (27). This nding was higher than the studies done in Menz Lalo district, northeast Ethiopia, 6.2 % (22) and Kenya 6.1% (20). However, the nding was lower than the results in Pakistan 20.8% (29), Israel 22% (30), Ghana 50.5% (31) and Senegal 72.3% (32).
The possible explanation for this discrepancy might be due to differences in study participant characteristics, study period, design and health service accessibility.
The nding was higher than the ndings in Menz Lalo district, northeast Ethiopia (26.4%) (22), and Kenya (28.2%0 (20). However, this nding was lower than as the studies conducted in Bangladesh (64%)(33), Ghana (50.5%) (31) and Senegal (72.3%) (32). The possible explanation for this discrepancy might be due to the differences in the study participants, access to vaccines, and variations in the recommendation of wastage rate to open BCG and Measles vaccines across countries (22). Besides, this study also revealed that 16.4% (95%CI: 13.3-19.8) of children were received measles vaccine earlier than the recommended time interval. The nding was higher than a study conducted in Bangladesh (12%) (33) and lower than a study done in Pakistan (90%) (29). The possible justi cation might be health workers' appointment before nine months of age to prevent open dose vial wastage, mothers/caregivers being too busy on appointment day and forgotten vaccination appointment (22).
The vaccination timeliness was lower in the higher dose of the antigen for those vaccines which had subsequent doses such as penta1-3, OPV 1-3, PCV1-3 and Rota1-2. This might be due to increased maternal/caregiver's workload with other domestic activities while the child gets older and they may not remember vaccination appointments of a child and fear of side effects (22,34).
This study also revealed that 5.5and 2.6% of children were received the vaccine earlier than the recommended time interval for Penta1 and penta3 vaccines, respectively. This nding was in line with a study done in Menz Lalo district, northeast Ethiopia 6.8 and 5.2% of children were vaccinated Penta1 and penta3 vaccines, respectively (22). On the other hand, 30 and 53% (95%CI: 49.3-57.6) of children aged 12 to 23 months were vaccinated later than the acceptable time interval for Penta1 and penta3 vaccines, correspondingly. This nding was lower than the ndings in Menz Lalo district, northeast Ethiopia, 54.1 and 64.5% of children were received Penta1 and penta3 vaccines later than the recommended time interval, respectively (22). However, this nding was higher than the studies done in Pakistan, 19.1 and 43.4% of children received Penta1 and penta3 vaccines later than the acceptable time interval , correspondingly (29). This discrepancy might be due to mothers/caregivers of children might not remember the appointment date, work load by domestic activities or fear of side effects like fever, pain and swelling.
Rural children were negatively in uenced the receiving of vaccines in the recommended age than urban children. This nding was in line with the ndings in Ethiopia (23). The possible justi cation might be due to urban resident mothers might have better information and recognize the importance of vaccination (37).
Children whose mothers gave birth at home were less likely to receive the recommended childhood vaccines in the acceptable time. This nding was supported by the studies conducted in Kenya (11), Ethiopia (23), Pakistan (29), Malawi (38) and Uganda (39). The possible justi cation might be mothers who gave birth at health facilities might have more opportunity to be informed about child healthcare, including childhood vaccination (29).
Children who were born from educated mothers were more likely to receive their vaccines timely than noneducated mothers. This nding was consistent with the ndings of the study done in Bangladesh (33).
The possible justi cation might be educated mothers might have better knowledge about vaccinepreventable diseases and recognize the importance of vaccination.
Children of mothers/caregivers having history of abortion before the birth of the index child were more likely to receive the recommended childhood vaccines with acceptable time interval. This might be due to mothers/caregivers with history of abortion give more emphasis for the health of their child, fear the morbidity of child and understood the burden of childhood infection more than their counterparts.
Children of mothers/caregivers with good knowledge about childhood vaccination were more likely to be vaccinated with the recommended time interval. This is in line with the ndings of a study done at Menz Lalo district, northeast Ethiopia (22). This can be suggested mothers/care givers having a better understanding of childhood vaccination schedule, vaccine preventable diseases and reasons for vaccination may bring their child to vaccination site more likely at recommended time. Children of mothers/caregivers with favorable attitude towards childhood vaccination were more likely to be vaccinated timely. This is in line with study conducted in Machakel district, east Gojjam zone (40). This can be suggested mothers/caregivers who had unfavorable attitude about childhood vaccination might not take their child to vaccination site by their appointment.

Limitations of the study
This cross-sectional study has its own limitations. The study participants were selected based on the presence of immunization cards, which might lead to selection bias because infants whose parents did not keep their immunization cards were excluded from the study. This could be over estimate or underestimate the magnitude of vaccination timeliness.

Conclusion
The overall childhood vaccination timeliness status was low compared with the current performance of the vaccination coverage in Ethiopia. Children were received the rst dose of OPV, Penta, PCV and Rota vaccines within recommended time relatively higher than the other doses/vaccines. Children received measles vaccine earlier and BCG vaccine later than the acceptable time interval. Variables such as residence, maternal level of education, having history of abortion, place of delivery, knowledge about childhood vaccination and attitudes towards childhood vaccination were affecting vaccination timeliness. Therefore, the policy planners and managers should give emphasis and incorporate vaccination timeliness in the childhood vaccination plan, and better to monitor and evaluate as one potential indicator to enhance the immune status of children. Health planners and managers should also improve women's education and awareness to enhance their attitude towards childhood vaccination to maintain and enhance to bring their children to their health facility in the appointment. Furthermore, it is better to promote institutional delivery service utilization to enhance childhood vaccination timeliness. Con dentiality during all phases of research activities was kept.

Consent for publication
Not applicable.

Availability of data and materials
All the data were included in the study, and data will be available upon a responsible request from the corresponding author.