A situational assessment of treatments received for childhood diarrhea in the Federal Republic of Nigeria

We assess progress towards improved case management of childhood diarrhea in Nigeria over a period of targeted health systems reform from 2013 to 2018. Individual and community data from three Demographic and Health Survey rounds are leveraged in a geospatial model designed for stratified estimation by venue of treatment seeking and State. Our analysis reveals a highly regionalised health system undergoing rapid change. Nationally, there have been substantial increases in the proportion of children under 5 years old with diarrhea receiving the recommended oral rehydration therapy after seeking treatment at either a health clinic (0.57 [0.44–0.69; 95% CI] in 2008; 0.70 [0.54–0.83] in 2018) or chemist/pharmacy (0.28 [0.17–0.42] in 2008; 0.48 [0.31–0.64] in 2018). Yet State-level variations in venue attendance and performance by venue have conspired to hold the overall proportion receiving this potentially life-saving therapy (0.45 [0.35–0.55] in 2018) to well-below ideal coverage levels. High performing states that have demonstrated significant improvements include Kano, Jigawa and Borno, while under-performing states that have suffered declines in coverage include Kaduna and Taraba. The use of antibiotics is not recommended for mild cases of childhood diarrhea yet remains concerningly high nationally (0.27 [0.19–0.36] in 2018) with negligible variation between venues. Antibiotic use rates are particularly high in Enugu, Kaduna, Taraba, Kano, Niger and Kebbi, yet welcome reductions were identified in Jigawa, Adamawa and Osun. These results support the conclusions of previous studies and build the strength of evidence that urgent action is needed throughout the multi-tiered health system to improve the quality and equity of care for common childhood illnesses in Nigeria.

This statement is required for submission and will appear in the published article if the submission is accepted.Please make sure it is accurate.This statement is required for submission and will appear in the published article if the submission is accepted.Please make sure it is accurate.This statement is required for submission and will appear in the published article if the submission is accepted.Please make sure it is accurate.Click here to access/download;Manuscript;main.pdf Jigawa and Borno, while under-performing states that have suffered declines in coverage include Kaduna and Taraba.The use of antibiotics is not recommended for mild cases of childhood diarrhea yet remains concerningly high nationally (0.27 [0.19-0.36] in 2018) with negligible variation between venues.Antibiotic use rates are particularly high in Enugu, Kaduna, Taraba, Kano, Niger and Kebbi, yet welcome reductions were identified in Jigawa, Adamawa and Osun.These results support the conclusions of previous studies and build the strength of evidence that urgent action is needed throughout the multi-tiered health system to improve the quality and equity of care for common childhood illnesses in Nigeria.

Introduction
Diarrheal illnesses are amongst the leading causes of childhood mortality in Nigeria, accounting for 16% of child deaths [1].Oral rehydration solution (ORS), a mixture of ber 12, 2023 2/16 clean water, salt and sugar, and preferably administered with zinc supplementation, has been shown to reduce the mean duration of diarrhea (by about 20%), mortality due to diarrhea (by 23%), stool output and the risk of a subsequent episode in the 2 to 3 months after supplementation [2][3][4].However, usage of ORS is reported to be low in most low-and middle-income countries [5,6].The use of recommended home fluid (RHF) was promoted by the World Health Organization (WHO) in addition to ORS and the combination is referred to as oral rehydration therapy (ORT).As a non-packaged home fluid alternative, RHF can comprise measured sugar and salt added to clean water or other home fluids such as rice water, coconut water, juice or tea [7,8].
Sustainable Development Goal (SDG) 3.8 is to achieve universal health coverage, including access to essential health care services and access to safe, effective, quality and affordable essential medicines for all.However, there has been slow progress in increasing access to simple and affordable treatments in Nigeria.The proportion of children with diarrhea who received either ORS or RHF increased from 31% to 42% over a ten-year period (2008-2018), while those for whom treatment was sought rose from 42% to 65% [9].These national figures, however, mask substantial local variations in common with other health indicators in Nigeria [10,11].About 3% of the children from Taraba state that had diarrhea in 2018 received ORS and zinc supplements compared with 72% in Nasarawa state [5].Appropriate and timely care-seeking in formal health facilities would allow for prompt and correct diagnosis, appropriate management and avert complications [12,13].

Many Nigerian mothers have adequate knowledge of what constitutes diarrhea and
could identify episodes of it in their children [14].But poor knowledge of the use of ORS and zinc supplementation has been identified as a major barrier to improving usage across different parts of Nigeria [1].There are mothers who hold the myth that diarrhea is a sign that the child is teething, which can negatively influence their health care decision making [1,15].A study in eight Nigerian States, and another in Oyo State, identified unavailability, unaffordability and poor awareness as the major barriers to ORS/zinc utilization [13,16].Encouragingly, consultation with a health worker, having a secondary or higher level of education and exposure to mass media were reported to encourage the use of ORT for the treatment of diarrhea [17].The ber 12, 2023 3/16 venue where treatment was sought also substantially affects the chances of receiving ORS or ORS and zinc supplementation across the country [13].
Because it is rarely microbially caused, the use of antibiotics for infectious diarrhea brings little benefit in most cases [18].The WHO guidelines on the treatment of diarrhea therefore discourages the use of antibiotics for treating non-severe cases, restricting its use to instances of bloody diarrhea and cholera with severe dehydration [19,20].Indiscriminate use of antibiotics leads to antibiotic resistance, capable of compromising the treatment of infectious diseases and undermining other advances in health and medicine [19].Over-use of antibiotics also leads to increased medical costs, longer hospital stays and increases the risk of subsequent diarrhea episodes because of its effects on gut microflora [21].Notwithstanding, studies have reported abundant use of antibiotics in treating mild cases of diarrhea in various parts of Nigeria [20][21][22][23].
We Information on child health and interactions with the local health system was collected for children under 5 y/o living in the surveyed households.Data concerning experiences of ill health were collected by questionnaire targeting events in the two weeks prior to the surveys, answered on the child's behalf by the mother or caregiver.
A child was identified to have suffered from diarrhea if the child had three or more loose or liquid stools in the same day (on one or more days of the preceding two weeks).Whenever a child is positively identified as having experienced diarrhea, the caregiver was asked if the child was given oral rehydration/ORS or antibiotic pills or syrups.If the child received any treatment, the caregiver was asked to indicate where the treatment was sought.The response variables for our analysis were constructed as binary indicators as for: (i) each of ORS/RHF and antibiotic, indicating whether or not the child was treated with any of these and (ii) each of treatment-seeking class indicating whether or not treatment was sought at a health facility (private or public facility), a chemist/pharmacy or treated at home.ber 12, 2023 5/16

Geostatistical Model
Given the multistage structure employed in gathering the DHS data, a key element in geostatistical modeling is to include the sampling characteristics in the model, as doing otherwise could potentially bias the estimates.We adopt a geostatistical technique for areal data that considers the stratified multistage cluster design used in data collection as proposed by Chen and colleagues [25].The approach proceeds by first computing the proportion for each location using a designed-based weighted (direct) estimator: where c = 1 • • • C are clusters sampled within strata, and for each cluster c, k ∈ s c is the indexes of individuals sampled in each cluster c.The binary outcome Y ck is the quantity whose prevalence is to be estimated, w ck are the sampling weights and s i is the indices of clusters sampled in area i.To enhance precision, a transformation of this weighted estimate can thereafter be modeled using a random effect model [26].
An approach for the binary outcome is to consider Z i = logit(p HT i ).If the design-based variance is denoted by V i , the model is are the spatial locations (States of Nigeria) that are assigned a spatial distribution.Thus, an intrinsic conditional autoregressive (ICAR) prior, following the assumption that in general, events at neighboring locations are likely to be similar, was adopted.We implement the model using the SUMMER package in R. The package is useful for small area estimation using survey data collected with complex stratification designs [27].The package builds on the R-INLA package using the BYM parameterisation for estimating the smoothed spatial effects [28].We chose 90% credible intervals to quantify the significance of our estimates.To compare changes in events between the previous years and 2018 for each State, we subtracted the estimated prevalence between the years compared, while to determine the significance in the change, we estimated the difference in the credible ber 12, 2023 6/16 intervals such that whenever (a) the upper 90% credible interval value for earlier year is greater than the lower 90% credible interval value for 2018 or (b) the lower 90% for the earlier year is lower than the upper 90% for 2018, the difference is said to be not statistically significant.

Results & Discussion
Treatment Seeking Venues or fewer of the children would be taken for treatment at a health facility among those who reside in Borno, Yobe, Taraba, Niger and Zamfara states while the estimates are not significant for the other states.This finding demonstrates the sub-optimal use of formal healthcare services for child health throughout the country and particularly among individuals in the northern fringes as revealed by previous studies [12,29,30].
Some authors attributed this to the prevailing cultural differences in perception of health and diseases, and the availability and distance to healthcare facilities [30].
In the case of chemist/pharmacy, a larger proportion of the children who live in Borno, Yobe, Bauchi and Kano states sought treatment for diarrhea at a chemist/pharmacy.Facing health service inacessibility and/or unaffordability the residents of these areas may turn to coping strategies such as praying to God, use of traditional medicine and patronizing unaccredited chemists [31].A systematic review reveals that in most low-and middle-income countries (LMIC) the majority of caregivers seek care for childhood illnesses but only a handful utilize formal care provider, with no care-seeking more common for diarrhea [32].

Oral Rehyrdation Therapy
We estimated the national prevalence for the use of ORS/RHF received from any location to be 0.41 (90% CI: 0.  management of childhood illnesses who were deployed to internally displaced persons (IDP) camps to treat children with mild ailments such as diarrhea, malaria and pneumonia while those with serious conditions were to be referred to nearby health facilities [35].There were also WHO-supported mobile health teams, a group of trained medical professionals who provide essential health services to vulnerable and displaced populations and host communities across states in the north east region [36].

Antibiotic Use
The national mean proportion of early childhood diarrhea cases treated with antibiotics was estimated to be 0.

Further Discussion
The treatment of childhood diarrhea in Nigeria has often been marred by poor knowledge of the use of appropriate low cost therapy [1].A consequence is the increase in the number of episodes that young children incur in a year.There is a widespread use of antibiotics without diagnostic or epidemiological reasons to justify the use [20,22].Over the years, different interventions by local and international authorities to improve life-saving health services particularly to the most vulnerable ber 12, 2023 10/16 population have been contemplated but these have yielded mixed impact at different communities [13].Thus, model-based estimates empower investigations at subnational levels, improving the understanding of local variations and trends and aiding targeted interventions.Geostatistical modeling endeavors in the Nigerian public health domain have therefore been of interest in recent years [10,11].
The findings reveal that for most of the States, including those that have enjoyed specific interventions to improve diarrhea treatment, not much change has taken place over the ten-year period, with Kaduna showing a negative change in the use of ORS/RHF but positive for antibiotic use.However, in a State like Borno that has witnessed civil unrest for more than a decade, the findings indicate that a larger segment of the children with episode of diarrhea would benefit from the recommended therapy, a development that can be attributed to the deployment of trained personnel who serve as mobile health teams that provide essential health services to vulnerable and displaced populations [36].For the majority of the States, the proportion of children with diarrhea for whom treatment was sought at a health facility was not significantly higher than the national average, although there is evidence that the use of ORS/RHF in Nigeria is shaped by the relative propensities of patients in different areas to seek care at health facilities.Consequently, a community-based approach as practiced in the conflict State of Borno can be considered in other parts of the country.

Conclusion
We have characterised spatial and temporal trends in the treatment seeking and treatment outcomes for episodes of early childhood diarrhea in Nigeria over the period 2008-2018 covered by three rounds of DHS surveys.While there have been substantial increases in the fraction of cases receiving treatment with recommended oral rehydration therapy at the national level, there has been substantial sub-national variation in these improvements, and antibiotics remain over-used in the treatment of diarrhea across Nigeria.While care seeking at a health facility is associated with an increased likelihood of receiving the recommended oral rehydration therapy, it is also associated with an increase likelihood of antibiotic treatment at a level equal to that of care seeking at a chemist/pharmacy.
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with the following details: Initials of the authors who received each award • Grant numbers awarded to each author • The full name of each funder • URL of each funder website • Did the sponsors or funders play any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript?• Gates Foundation [INV-009390 OPP1197730] Peter Gething was additionally supported through funding provided jointly by Curtin University, the Telethon Trust and the Telethon Kids Institute under project ID RES-61992 Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation Did you receive funding for this work?"Please select the country of your main research funder (please select carefully as in some cases this is used in fee calculation).as follow-up to "Financial Disclosure Enter a financial disclosure statement that describes the sources of funding for the work included in this submission.Review the submission guidelines for detailed requirements.View published research articles from PLOS ONE for specific examples.
with the following details: Initials of the authors who received each award • Grant numbers awarded to each author • The full name of each funder • URL of each funder website • Did the sponsors or funders play any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript?• Did you receive funding for this work?"UNITED STATES -US Competing Interests Use the instructions below to enter a competing interest statement for this submission.On behalf of all authors, disclose any competing interests that could be perceived to bias this work-acknowledging all financial support and any other relevant financial or nonfinancial competing interests.
change.Nationally, there have been substantial increases in the proportion of children under 5 years old with diarrhea receiving the recommended oral rehydration therapy after seeking treatment at either a health clinic (0.57 [0.44-0.69;95% CrI] in 2008; 0.70 [0.54-0.83] in 2018) or chemist/pharmacy (0.28 [0.17-0.42] in 2008; 0.48 [0.31-0.64] in 2018).Yet State-level variations in venue attendance and performance by venue have conspired to hold the overall proportion receiving this potentially life-saving therapy (0.45 [0.35-0.55] in 2018) to well-below ideal coverage levels.High performing states that have demonstrated significant improvements include Kano, set out to quantify trends by venue in treatment seeking behavior for childhood diarrhea among under-five children according to States of Nigeria.Our objective is to quantify progress in diarrhea treatment in the country over a ten-year period considering the various interventions and programs put in place over the years.For instance, the Essential Childhood Medicines Scale-up Plan (ECMSP) (2012-2015) was contemplated as the country's first national road map for increasing access to life-saving treatments[24].A program was then implemented by the Clinton Health Access Initiative (CHAI) to align with the proposed strategies and activities under the ECMPS in eight Nigerian states between 2013 and 2017[13].We used data from three waves of Nigeria Demographic and Health Surveys (NDHS) conducted in 2008, 2013 and 2018 and adopted a Bayesian geostatistical modeling technique that incorporates the sampling characteristics of the surveys.This allows for more accurate estimates of the treatment seeking behavior at State levels and provides actionable insight for policy makers at and above this adminstrative scale.ber 12, 2023 Materials and methods Datasets Data was compiled from three waves of the NDHS conducted in 2008, 2013 and 2018.Implemented by the Nigeria Population Commission with technical support from the DHS Program, these nationally-representative surveys offer quality assured cross-sectional data on a diverse collection of demographic and health indicators.The standardised methodology employed in each survey facilitates comparative analyses across time and space.A two-stage stratified cluster design was used for data collection.First, enumeration areas (clusters) were selected from a sampling frame created for the 2006 Population and Housing Census of the Federal Republic of Nigeria; and second, households were selected from each cluster by equal probability sampling.A total of 777, 904 and 1,400 clusters were randomly selected for the 2008, 2013 and 2018 surveys, respectively, from which representative samples of 34,070, 40,680 and 42,000 households were constructed.The response rates for the eligible women in each survey, who must be between ages 15 and 49 years, were 97%, 98% and 99%.

Fig ? ?
Fig ?? presents the results for treatment seeking-behavior for diarrhea, indicating whether treatment was sought at a clinic (Fig ??A) or at a chemist/pharmacy (Fig ??B).For all the maps, States shaded with dots are places where the estimates are not significantly different from the national average.The findings reveal that about 20%

Fig 1 :
Fig 1: Model-based estimates of the breakdown of treatment seeking for early childhood diarrhea in Nigeria by venue and State for 2018.
estimates for all the other States, including the FCT, are not significant.In Fig ??B, we compute change in the proportion of children with diarrhea who received the recommended ORS/RHS therapy since 2008, with the aim of measuring State-specific progress over the ten-year period.The findings indicate significant positive change in Sokoto, Katsina, Kano, Jigawa, Bauchi, Borno and Nasarawa States but negative in Kaduna and Taraba, implying reduction in the proportion of children with diarrhea who received the recommended therapy in these two areas.Katsina, Kano and Bauchi States might have been impacted by the ECMPS program undertaken by CHAI [13] but this was not the case for the other states covered by the program; of particular concern is Kaduna where the estimates indicate a negative change that was significant.The dramatically high usage in Borno, a state affected by conflict since around 2009, could be attributed to focused interventions from the international community.The WHO trained a number of community resource persons on integrated community case ber 12, 2023 8/16

Fig 2 :
Fig 2: Model-based estimates of the proportion of early childhood diarrhea cases receiving the recommended oral rehydration therapy in Nigeria by venue and State in 2018.Furthermore, we compute the differences in proportion of children who received recommended ORS/RHF based on the venue where treatment was sought, considering each venue against all other venues (Fig ??C, D, & E).The estimates suggest that the the use of ORS/RHS for treatment of diarrhea is modified by the place where treatment was sought.Specifically, with the exception of a few states namely, Borno, Nasarawa, Plateau, Ogun, Delta, Akwa Ibom and Rivers, where the estimates are not significant, the majority of the children from the other states for whom treatment was sought at a health facility would receive the recommended ORS/RHF.For those who sought treatment at a chemist/pharmacy, only Niger and Jigawa states show positive changes in the proportion of children who received the recommended therapy.Regarding the children for whom neither a health facility nor chemist/pharmacy was visited, the findings indicate negative change in the chances of receiving the recommended ORS/RHF in majority of the States, with no State having higher proportion in this category.Consequently, improvement in the use of ORS/RHF for treating diarrhea among children in Nigeria can be driven by care seeking at health facilities, similar to what was reported by Lam and colleagues [13].

Fig 3 :
Fig 3: Model-based estimates of the proportion of early childhood diarrhea cases receiving antibiotics in Nigeria by venue and State in 2018.

Fig 1 Fig 2 Fig 3
Fig 1 Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation and contact information or URL).This text is appropriate if the data are owned by a third party and authors do not have permission to share the data.
This statement is required for submissionThe authors have declared that no competing interests exist.Powered by Editorial Manager® and ProduXion Manager® from Aries Systems CorporationPowered by Editorial Manager® and ProduXion Manager® from Aries Systems CorporationThe data underlying the results presented in the study are available from (include the name of the third party • The data underlying the results presented in the study are available from The DHS Program https://dhsprogram.com/Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation [22]h East, Nigeria[20]while in another study, about half of the children used unprescribed antibiotics in Enugu[22].These point to the widespread use of antibiotics for acute diarrhea in the country.The estimates are also significantly high but to a lesser extent for those in Adamawa, Plateau, Jigawa, Katsina, Kogi, Ondo and Osun states.On the change in use of antibiotics since 2008, the results show negative changes in Adamawa, Jigawa and Osun states but positive in Taraba.For the differences in the proportion of children who received antibiotics when care was sought at a health facility against other venues, the results indicate that children who reside in Bauchi, Plateau, Kano, Jigawa, Adamawa, Zamfara and the FCT are more likely to receive antibiotics when treated at a health facility; those who lived in Kebbi, Sokoto, Kwara, Kaduna, Kano, Gombe, Yobe, Benue, Imo and Abia States and visited a chemist/pharmacy would more likely to have been given antibiotics.In the majority of the States, those who neither visited a health facility nor a chemist/pharmacy were less likely to have been treated with antibiotics.