Regional disparities and their contribution to the coverage of the tetanus toxoid vaccine among women aged 15–49 years in Indonesia [version 1; peer review: 1 approved, 2 approved with reservations]

Background: The prevention of Clostridium tetani bacterial infection through the administration of the tetanus toxoid (TT) vaccine in women is important. The purpose of this study was to determine the regional disparities and factors associated with TT vaccine coverage in women aged 15–49 years in Indonesia. Methods: The Indonesian Demographic Health Survey (IDHS) 2017 data was used in this study. A total of 36,028 women, aged 15–49 years were recruited using the two-stage stratified cluster sampling technique. The questionnaire used was based on the DHS Questionnaire Phase 7. Chi-squared and binary logistic regression were used in this study as part of the analysis. Results: We found that the TT vaccine coverage was 75.32% and that the majority were spread across several provinces. The provinces of Bali and Nusa Tenggara, the richer respondents, living in a rural area, visiting the health facility, having health insurance, and those currently working were factors making it more likely that the women would receive the TT vaccine. The respondents aged 15–24 years with a primary education level and the respondents who were divorced were less likely to receive the TT vaccine. Conclusion: The coverage of the TT vaccine among women can be increased by considering the regional disparities in Indonesia and the socio-economic demographic details of the respondents. Strengthening the policies from the central government in the local governments can improve the screening process and vaccine delivery outcomes. In addition, the importance of giving the TT vaccine to women needs to be relayed through health education in collaboration Open Peer Review


Introduction
Neonatal tetanus (NT) is a disease that can be prevented. It has become a global health problem with both high case and high fatality rates among neonates. 1 NT refers to tetanus that occurs at 28 days of early life. 2 NT occurs due to the toxins produced by Clostridium tetani alongside an unhygienic labor agent. It spreads through the umbilical cord. 3 One of the efforts to prevent the incidence of NT is the provision of an adequate tetanus toxoid (TT) vaccine for women of reproductive age. 4 In 2006, WHO developed guidelines for the TT vaccine for pregnant women to prevent NT. 5 The Indonesian government through the Ministry of Health Regulation number 42 of 2017 also launched the TT vaccine program as an advanced vaccine with a national and regional vaccine target coverage of at least 90% and 80%, respectively. 6 Two doses of the TT vaccine can provide immunity and reduce neonatal mortality by 94%. 7,8 One case-control study also reported that the administration of two doses of the TT vaccine was associated with a decrease in the incidence of NT 9,10 and vice versa. 11 Infant mortality was predicted to decrease by 46% after the mother received their first dose of the TT vaccine and by 45% after the second dose. 12 The Indonesian Health Profile data from the years 2013-2015 show the trend that not receiving the TT vaccine is the leading cause of neonatal mortality. [13][14][15] Although NT can be prevented by the TT vaccine, the number of cases is still high. Globally, it is estimated that as many as 3.6 million neonates die every year, among which 59,000 die from tetanus. 16 The infant mortality rate in Indonesia according to the Indonesian Demographic and Health Survey in 2007 was 34 deaths per 1,000 live births with the highest number of deaths occurring during the neonatal period. 17 The neonatal mortality rate in Indonesia in 2007 was 19 per 1000 live births and NT was one of the main causes of death. 18,19 There are still cases of NT in line with the coverage of the national and regional TT vaccines not yet reaching the target. Nationally, the coverage of the TT vaccine for both pregnant and reproductive age women tends to fluctuate and has not yet reached the target. The TT vaccine coverage for pregnant and reproductive age women from 2007 to 2011 was 26% and 27.1%, 65.2% and 24.7%, 73.5% and 11.2%, 69.5% and 8, 6%, and 63.6% and 11.8%, respectively. 17 If the regional data is examined randomly, the coverage of the TT vaccine in select regions has also not reached the target. 20 The low coverage of the TT vaccine is largely influenced by inadequate knowledge. 21,22 Women of reproductive age with knowledge of maternal and neonatal tetanus (MNT) and low TT vaccine are 0.435 times more likely to receive the TT vaccine. 23 Insufficient knowledge of the TT vaccine among prospective brides of reproductive age are one of the factors for the low TT vaccine coverage. 24 Based on the data above, to overcome this inadequate knowledge, health education about TT is needed. Good health education pays attention to and identifies people's characteristics in the intended category so then the health education provided can be more effective. 25 This study is focused on revealing TT vaccine coverage and the determinant factors of the TT vaccine being received in relation to women of reproductive age.
Several previous Indonesian studies have revealed the coverage and determinants of the TT vaccine. Research into the TT coverage is still reported on a regional scale. 26,27 Research on the determinants of the vaccine for women of childbearing age specifically includes knowledge, family support, attitudes, and the behavior of the health workers. 22,28,29 This study used available national data including age, education level, wealth quintile, residence, marital status, visiting the health facilities, health insurance, occupational status, the sex of the household head, pregnancy, and the different regional areas in relation to the TT vaccine. It is expected that the results of this study can be used when devising effective approaches for the education of women of reproductive age to promote the TT vaccine.

Study design
A cross-sectional study design was undertaken. We used secondary data from the Indonesian Demographic Health Survey (IDHS) 2017 and parts of the Inner-City Fund (ICF) International data.

Sample
The survey was conducted in December 2017. We used the IDIR71FL dataset (Indonesian Individual Recode phase 7). The total study population was 49,627 women aged 15-49 years. We then weighted the data based on the number of provinces in Indonesia in order to obtain the average for each region. We managed to reach 36,028 women aged 15-49 years who have not received the TT vaccine in Indonesia. Furthermore, there was missing data. Two-stage stratified cluster sampling was used in this study by selecting clusters from each stratum and a list of families from the selected clusters. Then the families' questionnaire responses were investigated (Demographic Health Survey, 2017).

Variables
The independent variables in this study included age, education level, wealth quintile, residence, marital status, visiting the health facility, health insurance, occupational status, sex of household head, pregnancy, regional disparities. Age was categorized into 15-24 years old, 25-34 years old and 35-49 years old (Health Ministry of Republic Indonesia, 2009). Based on Law No. 20 of 2003 concerning the National Education System in Indonesia, education level was categorized into high, secondary, primary, and no education. 30 The respondents' wealth quintile was categorized into poorest, poorer, middle, richer, and richest respectively. 31,32 Residence was categorized into either an urban or rural area. 33 Marital status was classified as either married, partnered, widowed, divorced or separated. The respondents who had visited a health facility in the last six months, whether they had health insurance, if they were currently working, and their pregnancy status were all categorized as either yes or no. 31 We identified the sex of the household head as either male or female. For the regions in Indonesia, we classified the country based on the big islands as follows: Sumatera, Riau, Java, Bali and Nusa Tenggara, Kalimantan, Sulawesi, Maluku, and Papua. 34 The dependent variable in this study was the TT vaccine. We identified women aged 15-49 years who either received or did not receive the TT Vaccine. Then we categorized them according to their answer of either yes or no (Demographic Health Survey, 2017). To enhance the quality and transparency of reporting the study results, the researchers applied The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). 35

Data analysis
We used the STATA version 16.1: "A Software resource for statistical analysis and presentation of graphics (Stata, RRID:SCR_012763)". We used Chi-squared to analyze the bivariate data and binary logistic regression to analyze the multivariate data. We used the adjusted odds ratio (AOR) with a 95% confidence interval (CI) and a significance level of p < 0.05.

Ethical considerations
Ethical approval for the secondary dataset was not required. The dataset policy is available on the official website. We received approval to use the dataset from ICF International with number AuthLetter_154679.

Results
In this study, we found that the coverage of the TT vaccine in Indonesia reached 75.32% out of the 36,028 respondents. More than half of the total respondents who received the vaccine aged 35-49 years were educated to secondary school level. The distribution of wealth quintiles was almost the same, ranging from poorest to richest. The majority were in the poorest quintile. In addition, the distribution of residence was almost the same across both urban and rural areas. The majority of the respondents in this study were married and they had regularly visited health facilities in the last six months. We found that the majority of respondents had health insurance, were working, and were not pregnant. The majority of the household heads were male. According to the regional data, the majority of the respondents were spread across the large islands in Indonesia such as Java and Sumatra (Table 1).
Upon examining the regional distribution data in Indonesia, the TT vaccine coverage was more than 70% in Riau, Java, Bali and Nusa Tenggara, Kalimantan, Sulawesi, and Papua. The majority of respondents aged 35-49 years were spread across Indonesia. The distribution data indicate that the majority of respondents were educated to secondary school level, followed by those with primary education. The majority of respondents in the richest quintile and living in an urban area in Riau and Java. The majority of respondents in the poorest quintile and living in a rural area were in Bali and Nusa Tenggara, Sulawesi, Maluku, and Papua. Most of the respondents were married, had health insurance, were working, were not pregnant, and the household head was male. The respondents in Riau, Maluku, and the Papua islands responded stating that they had rarely visited the health facilities in the last six months ( Table 2).
The bivariate analysis showed that the regional variables, age, education level, wealth quintile, residence, marital status, whether they visited the health facilities, health insurance, whether they were currently working, and the sex of the household head have a significant relationship with TT vaccine coverage in women aged 15-49 years. However, the pregnancy variable did not have a significant relationship with TT vaccine coverage (Table 3). Table 4 shows the results of the multivariate analysis. The data indicate that regional disparities, age, education level, wealth quintile, residence, marital status, whether they had visited the health facilities recently, and health insurance are likely to be associated with TT vaccine coverage in women aged 15-49 years in Indonesia. The regional data shows that the respondents in Bali and Nusa Tenggara are 3.363-times more likely to receive the TT vaccine than the respondents in Sumatera (AOR = 3.363; 95%CI = 2.997-3.773). The respondents aged -24 years old are 0.71-times less likely to receive the TT vaccine than those aged 35-49 years (AOR = 0.71; 95%CI = 0.653-0.772). Regarding education level, the respondents with a primary school level of education were 0.544-times less likely to receive the TT vaccine than the respondents with a higher level of education (AOR = 0.544; 95%CI = 0.494-0.599). Furthermore, the richer respondents were 1.645-times more likely to receive the TT vaccine than the poorest respondents (AOR = 1.645; 95%CI = 1.506-1.798). The respondents living in rural areas were 1.106-times more likely to have had the TT vaccine than those living in urban areas (AOR = 1.106; 95%CI = 1.044-1.173). Divorced respondents were 0.693-times less likely to receive the TT vaccine than married respondents (AOR = 0.693; 95%CI = 0.608-0.79). The respondents who had regularly visited a health facility in the last six months were 1.693-times more likely to receive the vaccine than those who had not (AOR = 1.693; 95%CI = 1.609-1.781). The respondents who had health insurance were 1.176-times more likely to receive the vaccine than those who did not (AOR = 1.176; 95%CI = 1.117-1.239). The respondents who worked were 1.147-times more likely to receive the vaccine than those who did not (AOR = 1.147; 95%CI = 1.088-1.208).

Discussion
In this study, we discussed the gap in the reception of the TT vaccine among women aged 15-49 years in Indonesia by looking at the regional disparities. We also were able to determine the contributions behind the achievement of the TT vaccine coverage in Indonesia as it stands. We found that regional disparities were significantly associated with TT vaccine performance. In addition, the factors of age, education level, wealth quintile, residence, marital status, whether they visited the health facilities, health insurance, and whether they were currently working also contribute to the TT vaccine coverage among women aged 15-49 years in Indonesia.
Regional disparities are one of the demographic factors that contribute greatly to the TT vaccine coverage among women. Indonesia, which is an archipelago region, can be an inhibiting factor regarding vaccine coverage. 36,37 Differences in culture, region, ethnicity, language, knowledge, and access are important factors to consider when seeking to facilitate access to a vaccine. 38,39 According to this study, the Bali and Nusa Tenggara regions have a greater chance of administering the TT vaccine to their respective populations than other regions. When viewed according to socio-economic development, Bali and Nusa Tenggara, which are included within Eastern Indonesia, are far behind compared with the Java, Sumatera and Riau. 40,41 However, it can be seen in this study that the respondents' awareness of the importance of the TT vaccine is very high. This is consistent with the previous research which states that vaccine coverage can be influenced by region, development, knowledge and self-awareness. 42,43 We found that the younger respondents, aged 15-24 years, were less likely to receive the TT vaccine than the respondents who were older (35-49 years old). A previous study showed that age is related to the knowledge of the importance of vaccines and the ability to make decisions. 44,45 Therefore, health education is needed among those of a young age about the importance of vaccines. In addition, in this study it is also known that this is less likely for those of a primary education level compared with those with a higher level of education. This is because with a good level of knowledge, TT vaccination coverage can be achieved. In this case, the government and health workers have an important role in distributing knowledge about vaccines to the public. The previous study has shown that vaccine performance is influenced by a good level of knowledge. 46,47 In this study, we found that economic status contributed to the achievement of TT vaccine coverage in women. It is known that respondents with a wealth quintile that is higher and those with a job are more likely to receive the TT vaccine compared with the respondents whose economic level is low and who do not work. Previous research has shown that the respondents with a stable income can easily access private and government health facilities and get vaccines. 48,49 In addition, the respondents who had health insurance were found to be more likely to receive the TT vaccine. This is because the respondent feels calm that their medical costs will be covered by their health insurance. Previous research has shown that with health insurance, vaccine coverage can increase. [50][51][52] In terms of the rural areas, the study found that the residents of these areas are more likely to receive the TT vaccine. This is related to the obedience of the rural population where doctors, nurses and midwives have been able to gain the trust of the community. 53 This closeness is also obtained through the routine outreach process used to engage with the community members. 54 The information obtained by the rural residents tends to be more centralized and there is no intervention from other sources such as the internet and minimizing false news; the information will be centered on the doctors, nurses and midwives visited at the health facility as a result. This is in contrast to the urban residents who prefer to obtain their healthrelated information independently. They tend to compare the results of the information obtained from the internet with that of the doctors, nurses and midwives at the health facilities. The gaps in the information obtained trigger doubts about the TT vaccine and in the end, there is a delay in getting the vaccine even after marriage.
This study found that the women who visit the health facility are more likely to receive the TT vaccine. Visiting the health facility will increase their information and knowledge related to vaccines. 55 In addition, each visit can increase their closeness and bond with the health workers. This can convince the women aged 15-49 years old to have the TT vaccine. Routine visits to the health facilities can also overcome obstacles that have previously been a barrier to vaccines, including a lack of knowledge and excessive concern about the side effects of the vaccine. Rumors circulating in the community regarding the TT vaccine can be explained through counselling during visits to the health facilities. One of the rumors is that the content of the vaccine material is not halal, so there is resistance from some women. Health workers like the doctors and nurses are needed to clarify the problem.
Those with a divorced status were found to be less likely to receive the TT vaccine. This is associated by the decrease or non-existence of motivation from a partner. Divorced women do not feel the need to receive the TT vaccine. This is because one of the goals of this vaccine is to reduce the risk of tetanus in women and their unborn baby. 56 If they are divorced, there is no need for the TT vaccine. Although the TT vaccine is actually a requirement before marriage takes place, this vaccine can be missed because of the assumption that you have received the vaccine before. There is still the assumption that the vaccine is not necessary.
The strength of our study is that it provides information on the TT vaccine coverage nationally while highlighting the regional disparities in Indonesia. The results of this study can become basic data for the Indonesian government to use to determine further policies to achieve an improved level of TT vaccine coverage among women. However, this study has limitations in that the researchers looked at the distribution based only on the major islands in Indonesia. Descriptions at the provincial level are needed for the formulation of more specific policies.

Conclusion
In this study, we found there to be a gap in the TT vaccine uptake among women aged -49 years old in Indonesia. Indonesia as a whole, which is an archipelago, is one of the considerations and constraints involved in the coverage of the TT vaccine among women. The findings of this study provide an overview about the TT vaccine coverage according to several factors such as the regional disparities and the respondents' socio-economic demographic information. Furthermore, the government can collaborate across different sectors between the central and local governments to achieve the desired TT vaccine coverage. Providing accurate and precise information about the TT vaccine needs to be promoted by healthcare workers in collaboration with the community through online methods to reach the urban population areas in Indonesia. An in-depth exploration with additional factors and sectors involved is needed in terms of the direction of further research. you mean by low tetanus toxoid vaccine? "0.435 times more likely to receive the TT vaccine": this is not a good interpretation of the odds ratio.

Data availability
I found some difficulty checking on some references, e.g references 6 and 27, as they were written in a different language.

Methods:
You need to elaborate more on methods as follows: Sample, lines 3-4: "We managed to reach 36 Table 4, line 2: "and health insurance", it is better to say "and having health insurance".

Discussion:
Paragraph 2, line 2: "Indonesia, which is an archipelago region, can be an inhibiting factor regarding vaccine coverage". This statement needs rephrasing and clarification.
○ Paragraph 2, lines 7-9: "However, it can be seen in this study that the respondents' awareness of the importance of the TT vaccine is very high. This is consistent with the previous research which states that vaccine coverage can be influenced by region, development, knowledge and self-awareness": "vaccine coverage can be influenced by region, development": From the context, it seems that you refer to a direct relationship. However, this contradicts your findings as vaccine coverage in Bali and Nusa Tenggara is high (83.66%), despite having a high percentage of the poorest (48.38%) and a relatively low percentage of the richest (10.94%).
○ "self-awareness": Self-awareness was not studied in this research and it is a totally different concept, I think you mean awareness of the disease and vaccine.
○ ○ "it can be seen in this study that the respondents' awareness of the importance of the TT vaccine is very high": Awareness of the vaccine and of its importance was not studied in this research, in fact, awareness of the vaccine and of its importance could just be some of the possible factors underlying high coverage rates. You may point to awareness as an inference not as a finding. Please note that awareness of the vaccine is not the same as awareness of the importance of the vaccine. ○ Paragraph 3: Why do you relate your studied variables as age and education to knowledge and you continue referring to it (knowledge) despite not being studied in this research? In fact, many other variables could underlie and explain high coverage, such as: applying a good coverage policy, life experiences and beliefs, culture, physicians' attitude and behavior regarding vaccine, availability and accessibility of vaccine, and social support/pressure. ○ Paragraph 3, line 7: "the previous study", which study? You put two references not one. ○ Paragraph 4, lines 1-2: "It is known that respondents with a wealth quintile that is higher and those with a job are more likely to receive the TT vaccine compared with the respondents whose economic level is low and who do not work": Paragraph 6: You found that women who visited the health facility were more likely to receive the TT vaccine, then you started explaining your finding. You gave a good interpretation, however, some information was repeated, e.g "Routine visits to the health facilities can also overcome obstacles that have previously been a barrier to vaccines, including a lack of knowledge and excessive concern about the side effects of the vaccine". This is a repetition of what you have just said. You may rephrase this paragraph to explain your point without redundancy. ○ Paragraph 7: The same comment as paragraph 6. Please rephrase this paragraph to avoid redundancy. ○ Paragraph 7, line 4 "Although the TT vaccine is actually a requirement before marriage takes place", please identify the regulations and policy of the Ministry of Health in Indonesia ○ regarding TT vaccination for females. Paragraph 7, line 5 "vaccine can be missed because of the assumption that you have received the vaccine before", isn't there vaccination cards or records to refer to by the health personnel to make sure that the female client has been vaccinated? Is vaccine given only in health facilities affiliated with the MOH or it may be administered in private clinics? Please clarify. ○ Paragraph 7, lines 5-6: "There is still the assumption that the vaccine is not necessary", you need to elaborate a little more on this point and identify the rationale beyond this assumption.

Conclusion
Line 1: "we found there to be a gap in the TT vaccine uptake among women aged -49 years old in Indonesia", if you mean the age group 35-49 then this conclusion contradicts your findings as this group is the highest in vaccine uptake. If you mean 15-49 then you need to explain your conclusion, especially that your results ( Table 2) and your Discussion ("However, it can be seen in this study that the respondents' awareness of the importance of the TT vaccine is very high") referred to the high TT vaccine coverage rates. ○ Lines 2-3: "Indonesia as a whole, which is an archipelago, is one of the considerations and constraints involved in the coverage of the TT vaccine among women", you need to clarify this point a little.

Is the work clearly and accurately presented and does it cite the current literature? Partly
Is the study design appropriate and is the work technically sound? Partly

If applicable, is the statistical analysis and its interpretation appropriate? Partly
Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Partly tends to be more centralized and there is no intervention from other sources such as the internet and minimizing false news; the information will be centered on the doctors, nurses and midwives visited at the health facility as a result. This is in contrast to the urban residents who prefer to obtain their health-related information independently. They tend to compare the results of the information obtained from the internet with that of the doctors, nurses, and midwives at the health facilities." In the Discussion section, please have a comment on any current public health efforts from the Indonesian government to increase immunization coverage? 10.

Is the work clearly and accurately presented and does it cite the current literature? Yes
Is the study design appropriate and is the work technically sound? Yes

If applicable, is the statistical analysis and its interpretation appropriate? Yes
Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes