Uptake of protective tetanus toxoid vaccine doses and maternal associated factors during pregnancy in armed conflict zone, hospital-based cross-sectional study

Background Vaccinating pregnant women with tetanus toxoid (TT) is crucial to prevent neonatal tetanus, reducing related deaths by 94%. In conflict zones with restricted access to deliveries, neonates face a fatality rate of 80%–100%. This study explores the uptake of protective TT vaccine doses and maternal associated factors during pregnancy in an armed conflict zone. Methods A hospital-based, descriptive, cross-sectional study was conducted of 357 pregnant women at delivery using simple random sampling. Data were collected through interviews with a structured questionnaire, and entered using Epi-data version 3.1, and exported using SPSS version 22 for further analysis. Binary and multivariable logistic regression analyses were used to identify significant variables for receiving protective TT doses during pregnancy at P < 0.05. Result In this study, 355 pregnant women were included, with response rate of 99.4%. The mean age of the participants was 27.65 ± 6.23 years. During the study period, 67.3% of pregnant women received a protective TT vaccine dose while 33.3% were missed due to escalated armed conflict. The dropout rates were significant from TT5 to TT2 (17.6%), TT5 to TT3 (11.9%), and TT5 to TT4 (6.1%). However, maternal associated factors for the uptake of the TT protective vaccine dose were identified, including being aged 36–49 years [adjusted odds ratio (AOR) = 3.7; 95% confidence interval (CI) 1.54–7.8; P = 0.001], completing high school (AOR = 3.05; 95% CI 1.5–8.9; P = 0.02), having an antenatal care follow-up (AOR = 9.4; 95% CI 2.9–24.3; P = 0.001), previous media exposure (AOR = 15.5; 95% CI 7.5–25.3; P = 0.001), and good maternal knowledge (AOR = 2.7; 95% CI 1.8–4.9; P = 0.02). Conclusion The uptake of the protective TT vaccine dose among pregnant women in a continued armed conflict area was low compared with previous study findings. Efforts should be made to increase vaccine uptake and reduce dropout rates by addressing both community and individual-level factors.


Introduction
Tetanus is caused by a neurotoxin produced by the bacterium Clostridium tetani and has a fatality rate of 80%-100% (1,2).Immunizing pregnant women or women of childbearing age with two doses of the tetanus toxoid (TT) vaccination can potentially reduce neonatal tetanus mortality by 94% (3,4).To prevent tetanus-related deaths, pregnant women should receive a minimum of three doses of tetanus-specific immunoglobulin (TIG) (5,6).The World Health Organization (WHO) recommends five TT vaccine doses for individuals with unknown immunization status (7).In the first pregnancy, two doses of the TT vaccine are recommended, with the first dose given during the first antenatal care (ANC) visit and the second dose administered 4 weeks later (8)(9)(10).This immunization provides anti-tetanus antibodies for both mother and infant antibodies, transferred across the placenta as IgG, offers protection, and with 0.1-0.15IU/ml is advised (1,2,11).
Globally, tetanus is a significant public health issue, especially in areas with low immunization coverage and limited access to clean deliveries.Each year, an estimated 3.3 million neonatal deaths occur worldwide, with 34,019 deaths attributed to tetanus, as reported by the WHO in 2017 (4,12).Each year, approximately 303,000 women die from pregnancy-related complications, leading to approximately 830 deaths per day, as per the latest estimates from the WHO (13,14).The majority (90%) of maternal and neonatal morbidity of tetanus occurred in countries in Southeast Asia and sub-Saharan Africa (15,16).In India alone, 14,751 cases of tetanus were reported in 2019 (17).
In Ethiopia during the civil war of North East Ethiopia (between July 2021 and 28 November 2023), the Amhara region was heavily impacted, with 50% of healthcare facilities damaged, resulting in interrupted maternal health services for 70,000 pregnant women (11, 22) and including 1.4 million displacements and 600,000 reported death (1,22).The civil war impacted delivery of the TT vaccination service in areas of conflict due to security issues and the destruction of healthcare facilities (7,10).Therefore, the aim of this hospital-based, crosssectional study was to assess the level of uptake of the protective TT vaccine dose and maternal factors during pregnancy in an armed conflict zone of Saint Lalibela.

Methodology Study area
A facility-based, cross-sectional study was conducted at St. Lalibela General Hospital between 16 February and 7 March 2023.Situated in Lalibela town, the hospital serves the capital of the Lasta Lalibela district in the North Wollo Zone of northern Ethiopia.It is located 622.5 km away from Addis Ababa and 310 km from Bahir Dare.The hospital provides healthcare services to a population of approximately 600,000 people annually.The study area was selected due to the long-lasting armed conflicts during the civil war, which resulted in numerous disruptions, including over 1,000 recorded civilian deaths and injuries in the region.

Study design
A hospital-based, cross-sectional study was employed among 357 pregnant women in St. Lalibela General Hospital.

Inclusion criteria
All pregnant women receiving delivery services at St. Lalibela General Hospital during the study period were included in the interviews.However, mothers who were not pregnant and seeking maternal and child health services, including family planning or care for illnesses, at the hospital were excluded from the study.

Operational definition
Uptake of the protective TT vaccine dose refers to the protection provided to pregnant women who have received at least two doses of TT (2,23); or tetanus toxoid protective dose immunization (TTPDI) is defined as the proportion of mothers who have received any of the following documented TT doses: (1) two TT injections during the pregnancy; (2) two or more injections, with the last one administered within 3 years of the birth; (3) three or more injections, with the last one administered within 5 years of the birth; (4) four or more injections, with the last one administered within 10 years of the birth; or (5) five or more injections at any time before the birth (2).

Neonatal tetanus
Neonatal tetanus typically occurs within 3-21 days of birth and is caused by the introduction of tetanus spores through the umbilical cord during delivery, often as a result of using unclean materials to cut the cord (24).

Mass media exposure
Reproductive-aged women were asked about their exposure to TT vaccine messages through television, radio, newspaper, and mobile messages.To simplify the analysis, a variable called "exposure to mass media messages" was created, coded as "yes" if respondents had previous exposure to these messages (25).

Dependent variables
The dependent variable in this study is TT vaccine uptake (Yes/No).

Independent variables
The independent variables included sociodemographic factors (age, marital status, level of education, occupation, residence, and income), obstetric and related factors (nulliparity, planned pregnancy, pregnancy-related complications), health and healthrelated factors (distance from the health facility, ANC follow-up), and media exposure.

Sample size calculation
The sample size of this study was estimated using a single population proportion formula: n = (z 2 × p × (1 − p))/d 2 .Based on a prevalence of 69.8% reported from Gondar University Hospital in 2019 (10), with a 95% confidence interval (CI; z = 1.96) and a margin of error of 5% (d = 0.05), the formula yielded a sample size of approximately 324.Finally, after considering a nonresponse rate of 10%, the final sample size was 357.

Methods of data collection technique
Pregnant mothers who received immediate postnatal care were interviewed, excluding severely deaf and mentally ill individuals.The questionnaire was prepared in English and translated into Amharic.Face-to-face interviews were conducted using the Kobo Toolbox, involving data collectors, supervisors, and investigators.The interview questions covered sociodemographic data, conflictrelated factors, health facility-related information, and TT vaccination.A pre-test was conducted at Woldia Health Centre with 18 mothers (5% of the sample size) to ensure questionnaire consistency.The questionnaire was translated back to English from Amharic to ensure understandability and consistency.Data collection was carried out by a public health supervisor and two trained nurses.The interview questions focused on sociodemographic data, such as age, marital status, educational status, occupation, economic status, residence, number of children, and ANC follow-up, vaccination information, distance from the health facility, media exposure related to vaccination, and history of previous ANC follow-up and immunization.

Data processing and analysis
Data were checked for completeness and consistency before analysis.The Kobo toolbox was used for data collection, and the collected data were exported to SPSS version 25 for further analysis.The descriptive analysis determined means, frequency, and percentage distributions.Bivariate and multivariable logistic regressions were conducted.Independent variables with a p-value < 0.25 in bivariate logistic regression were included in the multivariable logistic regression, considering collinearity and data normality using a stepwise backward elimination procedure.The model's fitness was assessed using the Hosmer-Lemeshow goodness-of-fit test.Categorical variables with adjusted odds ratios (AOR) and 95% CIs were selected as determinants of TT vaccine coverage at p < 0.05.Knowledge about the TT vaccination was assessed using nine structured questions, and a mean score was calculated.Scores below the mean were considered poor knowledge, while scores above the mean were considered good knowledge.The Cronbach alpha test was conducted, and the overall knowledge-related assessment questions yielded a p-value of 0.76 (12,26,27).

Sociodemographic characteristics
Out of 357 postnatal women, 355 were interviewed, resulting in a response rate of 99.5%.The participants had a mean age of 27.65 ± 6.23 years, with the majority (72.4%) in the age range of 26-34.Of the participants, 91 (37.3%) had completed primary education or higher.Over half of the participants (91.5%) were married, with 220 (62.2%) being housewives.The majority of  1).

Maternal and health service-related factors
Of the total participants, majorities 267 (71.6%) of women had response for planned pregnancies and received support from their families.Moreover, 298 (83.5%) postnatal women were multiparous women, 70 (33.8%)completed fourth ANC visit, but 59 (16.6%) did not have any ANC follow-up.

Knowledge about the TT vaccine
The majority of participants (84.5%) were aware of the benefits of the TT vaccine, with 80.6% knowing that it is free of cost.In addition, 52.3% of participants had previous exposure to media messages about the importance of TT vaccine uptake.More than half (64.5%) believed that the TT vaccine had dual benefits for infants.Furthermore, 81.7% were aware that tetanus can be caused by unsafe delivery and injuries.Lastly, 73.5% of participants had good knowledge about the recommended TT vaccination dose for the protection of neonates and mothers (Table 2).

Impact of armed conflict on protective TT dose and dropout
In this study, more than half of the participants 258 (57.5%) experienced food insecurity, and 16.3% (59) lost at least one family member during the escalated war of Tigray people liberation front (TPLF) with Northern parts of Amhara region (Table 3).
During the interview, significant dropout rates were observed across different TT uptake intervals, with 17.6% from TT5 to TT2, 11.9% from TT5 to TT3, and 6.1% from TT5 to TT4, attributed to reasons such as war outbreaks (41.6%), forgetting their schedule (31.4%), and fear of side effects (28.2%), indicating notable variation in TT vaccine uptake interval (Figure 2).

Maternal associated factors for uptake of the protective TT vaccine dose
In the regression analysis, variables associated with the coverage of a protective dose of TT vaccine were identified using a significance threshold of p < 0.25.Eight variables, including age, residence, pregnancy status, level of education, occupation, number of ANC visits, and marital status, were included in the final multivariable logistic regression model.The results showed that age, knowledge of the TT vaccine, previous mass media exposure, level of education, and fourth ANC follow-up status were significantly associated with achieving protective TT doses within a 95% CI.Specifically, mothers aged 15-25 years were 3.7 times more likely to receive the protective dose compared to those aged 36-49 years (AOR = 3.7; 95% CI 1.54-7.8;p = 0.001).Completing high school or above (AOR = 3.05; 95% CI 1.5-8.9;p = 0.02), having the fourth ANC follow-up (AOR = 9.4; 95% CI 2.9-24.3;p = 0.001), exposure to media for TT (AOR = 15.5;95% CI 7.5-25.3;p = 0.001), and having good knowledge (AOR = 2.7; 95% CI 1.8-4.9;p = 0.02) were also significantly associated with achieving the protective dose of TT2 during pregnancy (Table 4).

Discussion
Tetanus is a vaccine-preventable disease that can occur in all populations, with neonates and pregnant women at highest risk.Ethiopia has the highest maternal and neonatal tetanus morbidity and mortality rates and only 49% of mothers get vaccinated with adequate tetanus toxoid in Ethiopia (3).Despite growing recognition of the detrimental effects of conflict on maternal and child healthcare, the literature is bereft of studies robustly quantifying the association between conflict and TT protective dose uptake of pregnant women during ANC service in Ethiopia, particularly in the Amhara region (8,9).The continued civil war in Ethiopia, specifically in the Amhara region, has led to extensive damage to healthcare facilities, disrupting maternal health services for more than 70,000 pregnant women, causing 1.4 million displacements and 600,000 reported deaths (11,22).
The conflict affected the delivery service of TT vaccination services due to security concerns, disrupting resource allocations, and facility destruction.This study estimated the level of TT vaccine uptake and maternal associated factors during the escalated war in St. Lalibela Hospital.
On the other hand, the final report of this study is lower than previously reported in the Lao People's Democratic Republic (79.7%) (31) and in Nigeria (81.1%) (32).The variation in TT vaccine coverage rates could be attributed to cultural differences, health-seeking behavior, healthcare coverage, economic and infrastructural access, and the impact of war.In our study, out of 296 pregnant women who initiated ANC before the war outbreak, 239 (67.1%) received a protective dose of the TT vaccine, while only 23 (6.4%) completed the full TT vaccination.In addition, 270 (76.3%) pregnant women were temporarily displaced from their residences during the war (16).
On the other hand, there was a significant TT dropout recorded at each TT uptake interval; this revealed the overall dropout rates from TT5 to TT2 (TT5-TT2), from TT5 to TT3 (TT5-TT3), and from TT5 to TT4 (TT5-TT4) were 17.6%, 11.9%, and 6.1%, respectively, with significant variation among each consecutive interval of TT vaccine uptake for pregnant women.This is consistent with the findings in previous studies conducted among pregnant women with TT vaccine uptake in TT vaccine protective dose uptake by postnatal women in St. Lalibela General Hospital.Sudan (21) and Sierra Leone (33).The possible elucidation for this significant difference between each consecutive interval of TT vaccine uptake was related to the continued armed conflict in both Ethiopia and Sudan, which led to larger coverage of TT for pregnant women.Maternal factors associated with achieving a protective dose of the TT vaccine during pregnancy were identified; accordingly, pregnant women aged 15-25 years had a three times higher likelihood of receiving the protective dose compared to those aged 36-49 years.This is consistent with previous findings in the southern region (SNNR) (8) and in Sudan (1).The possible reasons for the increased likelihood of younger pregnant women, particularly those aged 15-25 years, to be more likely to receive the TT vaccine during ANC is due to their curiosity, attentiveness, and proactive approach toward their pregnancy and them actively seeking out the vaccine as they believe it offers crucial protection during pregnancy.
In this study, pregnant women who completed high school have a 3.05 times higher likelihood of receiving the protective dose compared to illiterate pregnant women.This report is consistent with previous findings in Ethiopia (13), Tigray, Ethiopia (20), Debre Tabor town (30), and a Somali region (6).When increased level of education the more likely hood of aware women about to importantly of TT vaccine protective doses for infant and increased the likelihood of intention to took it during pregnancy.
The findings of the study revealed that mothers who attended their fourth ANC visits were 9.4 times more likely to receive two doses of TT injection than mothers who attended fewer than two ANC visits.This is consistent with the findings of previous studies in southern Ethiopia (8), Amhara region, and Tigray region (14,20).This might be due to the pregnant mothers having regular ANC visits, the likelihood of receiving comprehensive healthcare services and completing the recommended TT vaccine doses, and increased contact time with healthcare professionals who provide mothers with valuable health information, which can positively influence their healthcare-seeking behavior.
There was a significant association between pregnant women and previous media exposure.This study found that mothers who were exposed to media about the importance of the TT vaccine were more likely to receive the protective dose (AOR = 15.5;95% CI 7.5-25.3;p = 0.001).This is consistent with a systematic review conducted in Ethiopia (13) and in previous national-level studies (3,9).This might be because media exposure increases awareness, knowledge, and accurate information about the benefits of TT vaccination during pregnancy.It helps address misconceptions and cultural beliefs, improves access to healthcare services, and builds trust between healthcare providers and pregnant women.
Consistent with previous findings in Egypt (34), Gondar (2), a Somali region (35), and Sierra Leone (33), pregnant women with a good knowledge of protective TT vaccination doses have a 2.7 times higher likelihood of increased uptake of protective doses compared with the pregnant group of pregnant women (AOR = 2.7; 95% CI 1.8-4.9;p = 0.02).This might be the pregnant mothers had regular ANC visits, the probability of getting comprehensive and completed the recommended healthcare service including, the probability of getting full TT vaccine protective doses had increased.Healthcare providers, public health campaigns, and educational initiatives play a crucial role in disseminating accurate information about the vaccine's benefits and safety.
Unlike the findings in previous studies (1,8,9,21), in this study, family income, displacement during war, and the number of families did not significantly affect the uptake of protective TT vaccine doses for pregnant women.However, the pregnant women's knowledge of the tetanus vaccine and their level of education significantly impacted the uptake of the vaccine, highlighting the importance of addressing these factors to improve immunization rates, reduce hesitancy, and promote a culture that values vaccination.
The present study has some limitations.The cross-sectional survey design makes it difficult to establish clear causal relationships between the factors described and uptake of the TT vaccine.Recall bias may have influenced the study's results, as participants did not present their vaccination cards during data collection.Nevertheless, the study offers valuable insights to inform the development of health education interventions targeting increased uptake of the TT vaccine among pregnant women in Ethiopia.

Conclusion and recommendation
The utilization of the protective TT vaccine dose among mothers in the study area was low.Factors that enhanced the protective TT dose included level of education, ANC visits, age of respondent, fourth ANC follow-up, media exposure, and good knowledge about TT.Low utilization of the protective TT vaccine dose among pregnant in the study area can be addressed by focusing on raising awareness about regular ANC visits, establishing mobile clinics or outreach programs for healthcare access, enhancing security through collaboration, conducting community-based education campaigns involving community and religious leaders, providing training on safe vaccine administration, fostering coordination among healthcare providers and organizations, supporting healthcare facilities, and recognizing the psychological impact of conflict and offering mental health support services.

FIGURE 2
FIGURE 2Distribution of dropped TT doses among postnatal women who received care at St. Lalibela.

TABLE 1
Socio-demographic characteristics of study participants in St. Lalibela General Hospital for protective doses of TT vaccine.

TABLE 2
Level of maternal knowledge about TT vaccine protective doses for participant s women in St. Lalibela General Hospital for.

TABLE 3
Burden of maternal individual characteristics factors during escalated war among participant women in St. Lalibela General Hospital, 2023.

TABLE 4
Factors associated with uptake of protective tetanus toxoid vaccine doses among mothers during pregnancy in St. Lalibela Hospital, North Wollo Zone, Northeast Ethiopia.