Adherence to Intermittent Preventive Treatment of Malaria in Pregnancy with Sulfadoxine – Pyrimethamine and Associated Factors : A Cross-Sectional Survey in Benin ’ s Public Hospitals

RESEARCH ARTICLE Adherence to Intermittent Preventive Treatment of Malaria in Pregnancy with Sulfadoxine–Pyrimethamine and Associated Factors: A Cross-Sectional Survey in Benin’s Public Hospitals. Aguemon Badirou, Damien Barikissou Georgia, Padonou Sètondji Géraud Roméo, Kouwanou Modeste Luc and Ouendo Edgard Marius Department of Public Health, Faculty of Health Sciences, University of Abomey-Calavi, Cotonou, Bénin Regional Institute of Public Health (IRSP), University of Abomey-Calavi, Ouidah, Bénin


INTRODUCTION
Malaria is a major public health problem with substantial risks for the mother, her fetus and the neonate, particularly in highly endemic countries in most of the sub-Saharan Africa.More than 90% of the total malaria deaths occur in this region [1].In Benin, malaria is the leading cause of care-seeking, hospitalization and death, with 40.6%, 29.2% and 26% of cases recorded [2] in 2013, respectively.Pregnant women and infants are the most affected with higher mortality and morbidity.Malaria is the most frequent infection during pregnancy worldwide [3].It remains one of the major causes of mother and infant health degradation in hyperendemic areas of Plasmodium falciparum transmission [4].
Since 1990, preventing malaria during pregnancy has been based on the weekly administration of chloroquine prophylaxis in sub-Saharan Africa [5].This strategy resulted in a limited efficiency due to limited adherence to treatment outside the medical community and the development of resistance to chloroquine in P. falciparum [6,7].The World Health Organization (WHO) has therefore, developed and recommended a new strategy: Intermittent Preventive Treatment (IPTp) of Sulfadoxine-Pyrimethamine (SP) during pregnancy (IPTp-SP) to daily or weekly replace chemoprophylaxis with chloroquine for some women in pregnancy antenatal care.
IPTp-SP is an integral part of the World Health Organization's (WHO) three-pronged approach to the prevention and treatment of malaria during pregnancy, which also includes the use of Insecticide-Treated Nets (ITNs), and a rapid and effective case management [8,9].Until 2012, IPTp-SP consisted of administering at least two doses of SP to pregnant women spaced in time by at least a month [8].Updated in October 2012 by the WHO, the IPTp-SP is now recommended for all pregnant women at each Planned Prenatal Consultation (PPC) from the second trimester to the delivery period, if doses are administered at least a month apart [9 -11].Through the National Malaria Control Program (NMCP), Benin has adopted this intervention since 2004 and the implementation has been effective since 2006 [12].
In countries where the IPT-SP has been implemented for several years, studies show that the rate of the second-dose intake was remarkably lower [8, 13 -15].In Benin, recent studies reported an improvement in the coverage of IPTp-SP since its adoption, ranging from 3% in 2006 [16] to 35% in 2008 [17] and to 46% in 2010 [18].Nevertheless, the coverage of the IPT-SP is far from satisfactory, as it is still below the NMCP target of 100% of pregnant women receiving full IPTp-SP in 2015 [19].Furthermore, Benin performance is far from the new recommendation of WHO which requests five IPT-SP doses during pregnancy.This study aimed to measure the adherence rate to IPTp-SP for mothers and identify its determinants for decision-making.

Study Area
The study was conducted in two gynaecological and obstetric departments in Cotonou: the University Clinic of Gynaecology and Obstetrics (CUGO) of the National University Hospital of Cotonou (CNHU-HKM) and the Gynaecology and Obstetrics Department of the Mother and Child Lagoon Hospital (CHU-MEL).The CNHU-HKM and the CHU-MEL are the two referral centres for Gynaecology and Obstetrics in Benin.
Services offered in the facility include family planning, antenatal care, delivery, postnatal care, child welfare clinic, laboratory and pharmacy services.

Study Design
A cross-sectional hospital-survey was carried out over a period of three months from July to September 2015.

Sample Size Estimation
The sample size for the study was calculated using Schwartz's formula: n = Z 2 pq/i 2 .Where, Z = 1.96 at 95% confidence interval, p = 60% (IPT2 coverage in Benin in 2014) [20], i = precision level of 0.05 and q = 1 − p.The required sample size estimated was 368.

Inclusion/exclusion criteria
All the women with the following characteristics were eligible for participation: (i) had delivered in one of the two hospitals during the study, (ii) was still hospitalized at the time of the study, (iii) have had at least one prenatal consultation conducted by a health worker at any health facility in Benin and (iv) have given free and written consent to take part in the study.Those who had a postpartum pathology and / or complications were not included.
The dependent variable was defined as a person who took at least two doses of SP during the last pregnancy.We adopted this definition because the last WHO recommendation, requiring a dose of IPTp-SP in all consultation from the second trimester of pregnancy (a total of five doses), was not yet appropriately distributed in Benin.The independent variables were related to sociocultural and socio-demographic factors of the respondents, their obstetric history, their knowledge on malaria and IPTp-SP, the perception of the conduct of NPCs by the respondents and the awareness of the IPTp-SP and health care supply.

Data Analysis
Data were analysed using EPI INFO 7.0 version.The mean, median and standard deviation were determined for the quantitative variables.The proportions were calculated for qualitative variables.We used the Chi-square test to compare two proportions when the theoretical numbers were at least 5 and the fisher test when theoretical numbers were more than 5.To identify the factors associated to the adherence to at least two doses of SP during the last pregnancy, univariate and multivariate logistic regression analyses were performed.At the end of the bivariate analysis, the independent variables associated with the observance of IPTp-SP with a p-value less or equal to 0.20 were introduced in the logistic regression model.The Odd Ratio (OR) was used to estimate the association between the dependent variable and the independent variables.A significant threshold of 5% was considered.

Sample Description
A total of 366 women who gave birth were involved in the survey, including 48.63% at CUGO (at the CNHU-HKM) and 51.37% at CHU-MEL.The mean age of women was 28.12 ± 5.52 years.The age group 25-34 was the majority (60.93%).In terms of marital status, women in common-law unions were in the majority, accounting for 65.30% of the sample.Most of the women surveyed lived in urban areas, with 47.27% in Cotonou and 34.15% in other cities.Women in trade and craft sectors accounted for 27.05% and 24.32% of the sample, respectively.Regarding the distance between their homes and the health facilities, 54.92% of the women travelled more than 5 km.Women with no formal education on one hand and those with primary education on the other hand, each accounted for 24.59%.The ethnic groups, most represented among the women in the sample were the Fon and relatives with 38.8% and Adja and relatives with 26.23%.Concerning the religion of women, Catholics come first with 46.72% followed by Evangelicals with 29.51%, and Muslims with 11.48% of the total.
For gynaecological history, 36.07% of women were primiparous and 27.87% of the primigravida (Table 1).

Adherence Rate IPTp-SP
The proportion of women taking at least two doses of SP during pregnancy was 63.11%.This rate was 62.92% and 63.30% at the CNHU-HKM and the CHU-MEL, respectively.

Determinants of Adherence to IPTp-SP
In univariate analysis, age, marital status, religion, place of residence, distance from home and health facility, level of education and customary prohibitions of medication use during pregnancy are not significantly associated with adherence to IPTp-SP.Only the need for a third-party authorization to monitor pregnancy showed a significant association with adherence to IPTp-SP, p-value = 0.0030 (Table 2).No factors related to the obstetric history of the respondents were significantly associated with adherence to IPTp-SP in this study (Table 3).Women's adequate knowledge of malaria prevention measures during pregnancy (p-value <0.0001), the number of tablets per dose of IPTp-SP (p-value <0.0001), and the number of doses of IPTp-SP to be taken during pregnancy (p-value <0.0001) were significantly associated with adherence to IPTp-SP (Table 4).Among the health-related factors, only participation in a IPTp-SP information session was significantly associated with adherence to TPIp-SP, p-value <0.0001, (Table 5).In multivariate analysis, four variables were selected in the final model.These four variables remained associated with adherence to the IPTp-SP adjusted to each other.The women who had adequate knowledge of the doses of IPTp-SP to be taken during pregnancy were 4.70 times more likely to respect the adherence to IPTp-Sp compared to the women who did not have adequate knowledge.The variable "participation of women in an information session on the IPTp-SP during pregnancy" was 4.61 times more likely to adhere to the IPTp-SP compared to women who did not participate to an information session.Similarly, the comprehensive knowledge of the number of tablets per dose of IPTp-SP multiplies the chance of adherence by 3.32.Finally, women who had adequate knowledge of malaria prevention measures during pregnancy were 2.56 times more likely to adhere to ITPp-SP than those who did not have comprehensive knowledge (Table 6).

DISCUSSION
We obtained almost the same defiance IPTp-SP rates at the University Hospital-HKM of Cotonou and the University Hospital "Mother and Child Lagoon" (CHU-MEL) with 62.92% and 63.30%, respectively.This similarity is justified by the fact that these two places are the referral in Benin and receive women with almost the same profile.The overall adherence rate was 63.11% for the entire sample.This rate, although rather good, is far from satisfactory, as it is still far from the objective of the National Malaria Control Program (NMCP) in Benin, which is to reach a 100% coverage for the second dose of the IPTp-SP in 2015 [19].
The adherence rate to IPTp-SP was higher than those reported by the 2011-2012 Demographic Health Survey (DHS) in Benin [19] and by the WHO in 2014, based on data from 2013 [1].The DHS 2011-2012 reported a rate of only 23% taking at least two doses of SP during pregnancy.As for the World Malaria Report published by the WHO in 2014, it reported an overall rate of 43% worldwide.This reflects an evolution of efforts to improve adherence to IPTp-SP in Benin.A lower rate of 52.5% was observed in the health zone of Pobè/Adja-Ouèrè/Kétou [21] in 2012.Earlier in 2009 [12], in a study carried out in eight maternities in Benin, the adherence to IPTp-SP that was almost similar to that of the present study (68.43%) was noted.Globally, it seemed that the adherence to IPTp-SP has increased in the health centre survey in Benin.
In a survey conducted in Tanzania in 2012 [22], the adherence rate of IPT-SP was estimated at 28.5%.In Malawi [23], however, a higher adherence rate of 72% was observed in 2009.Furthermore, in this study, only 18.03% of respondents took a minimum of three doses of IPT-SP during pregnancy.This rate is comparable to the World Malaria Report published by the WHO in 2014, which was 17%.Since it has been recommended to take a monthly consultation as from the 3rd month of pregnancy, five doses of IPTp-SP should be given to pregnant women according to the WHO recommendation.Then, Benin NMCP recommendation for IPTp-SP on pregnant women moved from two doses to tree doses since 2016.This new recommendation is not yet evaluated; however, efforts should be undertaken by the NMCP to disseminate this recommendation for better adherence.
Regarding the determinants of IPTp-SP adherence, three of the identified determinants were related to the knowledge on malaria prevention, and more specifically on IPTp-SP.This finding is in accordance with those of other authors [23 -25] who have shown a poor knowledge of women on IPTp-SP, particularly the number of tablets per dose.In addition, they identified other factors such as low antenatal coverage and prenatal consultations in the private sector.Thus, according to one of these studies, good knowledge on the use of SP during pregnancy was significantly predictive of good adherence to IPTp-SP [25].In 2010, in Nigeria, another study showed that women's comprehensive knowledge of malaria including its prevention during pregnancy through the use of IPTp-SP was associated with good adherence to IPTp-SP [25].All this confirms that adequate knowledge on IPTp-SP by pregnant women could improve their adherence.better communication strategy for Behaviour and Social Change needs to be implemented in order to improve women's knowledge on IPTp-SP.
The participation of women in communication sessions on IPTp-SP has also been shown in our study to be a determining factor in adherence to IPTp-SP in our study population.In 2012, in Tanzania, an almost similar result was observed [22].Indeed, the fact that informing women about the dangers of malaria during pregnancy was the main determinant of adherence to the IPTp-SP.The communication sessions, individual or collective, can improve women's knowledge on the IPTp-SP and therefore, promote better adherence to this strategy.The lack of communication to social and behaviour change may be related to a low quality of prenatal care services, as these services are responsible to inform the pregnant woman about the IPTp-SP, and its use during pregnancy.However, more than 90% (331 of 366) of the pregnant women surveyed were followed by qualified health workers (doctor or midwife).Prenatal care providers should be more aware of the health services they addressed to women, and more specifically concerning the IPTp-SP recommendations.Mass and health facility communication for social and behaviour change are mainly concerned.The health system must develop, and ensure their implementation.
Previous studies have identified other factors associated with adherence or non-adherence to IPTp-SP.This is evidenced by the WHO 2014 World Malaria Report [1], which found that poverty was the main determinant of nonadherence to IPTp-SP.Age below 20 years, lack of formal education, rural life and parity superior to one were also identified as negative influences on IPTp-SP adherence.On the other hand, a study carried out in Nigeria in 2010 showed that the primiparae adhered better to the IPTp-SP compared to the secondipares and the multipares [14].In Uganda between 2008 and 2009, a cross-sectional study on 500 women who were pregnant the previous year revealed that women were more likely to observe IPTp-SP if administered during the prenatal consultation [26].

CONCLUSION
The study found that raising and improving women's knowledge on malaria are necessary to achieve ITPp-SP adherence.Particular emphasis should therefore be placed on communication for social and behavioural change on pregnant women, family decision-makers, community leaders and health workers.