Assessing the Infection Burden and Associated Risk Factors in Children under 5 Across Jaipur's Urban Slums: A Feasibility Study Using a One Health Approach

slum environments. Abstract: given in four separate paragraphs, is a summary of that has been described in the Abstract Purpose: Infectious diseases are one of the leading causes of death among children under five (U5s) both in India and globally. This is worse in slum environments with poor access to water, sanitation and hygiene (WASH), good nutrition and a safe built environment. Globally, a One Health (i.e. human, animal and environment) approach is increasingly advocated for by the WHO-FAO-OIE tripartite to reduce infections and antimicrobial resistance. As under-5s living in peri-urban slums are exposed to household- and community-owned companion and livestock animals and pests, the CHIP consortium hypothesised that employing a One Health approach to co-produce behavioural change and slum upgrading interventions may reduce this burden where other WASH and nutrition interventions have failed. This study aimed to assess the feasibility of employing a One Health approach to assess under-5 infection and risk factor prevalence in Jaipur’s peri-urban slums, prior to undertaking prospective cohort studies involving culture and culture-independent sampling of under-5s and animals across our study sites in Jaipur (Rajasthan, India), Jakarta (Indonesia) and Antofagasta (Chile). Methods : We administered a rapid household survey to 25 purposively selected households across six slums in Jaipur. The questionnaire used evaluated infection prevalence, health-seeking behaviours, the built environment, the presence of companion and livestock animals and pests, and individual- and household-level demographics. We displayed the correlations between infection incidence and a range of factors in our sample, and displayed the portion of children under 5 who experienced one or multiple episodes of ill health, categorised by a range of One Health factors. Results: Parents reported at least one recent episode of ill health for a large portion (40%) of under-5s within the last 30 days. 80% of under-5s had no access to safe drinking water; every household reported the presence of at least one kind of pest within the respondent’s own home; and 20% of under-5s’ feeding equipment was cleaned with water only. Only one household reported owning a companion or livestock animal, potentially reflecting confusion about the definition of these animals. The incidence of infection appeared to be related to WASH and socio-economic factors as expected. : Safe drinking water, pest control and behavioural change surrounding the cleaning of under-5 feeding equipment should be given consideration in future research in this locale. Future studies should not rely solely on parent reporting of children’s symptoms – cross-referencing symptom reporting from multiple household members should be combined with culture and culture-independent sampling. Where possible, researchers should measure the presence of companion and livestock animals directly to avoid misinterpretation and to observe practices rather than relying on reporting alone. Childhood Infections and Pollution (CHIP) Study: Using citizen science to prevent


RE: Assessing the Infection Burden and Associated Risk Factors in Children Under 5 across Jaipur's Urban Slums: A Feasibility Study Using a One Health Approach
Thank you for your consideration of our manuscript. Here we attach a letter in response to the peer review comments and the Editor's comments.
We were grateful for your comprehensive comments. The paper is returned with changes made. Following the points made by the reviewers, the paper has been largely rewritten, and so changes made were not highlighted. Rather, we detail below the changes made.

Comments from Mustafa Abbas
Thank you very much for your submission to UCL Open Environment. It was a pleasure to read your work and consider your approach and points raised. You present what you describe as a feasibility study for a future longitudinal data gathering project via the CHIP consortium and aim to argue the need and usefulness of such research. I've had the opportunity to study your piece and I do have three areas of major issue that encompasses most of the paper, but I have included a fourth segment at the end on what I think you can do to make this a very valuable essay for the international health and environment community. Many thanks.
>>>> Thank you for your consideration of the manuscript and for your comments. We have made every effort to incorporate them, as detailed below.
1: I think major the first thing to say is that you have not justified the need for such a future longitudinal project and reading through I do not see a basis for such research. It is quite clearly known the relationship between WASH and U5 mortality and morbidity, as you correctly cite in your discussion. What do you hope to add? Based on your investigative >>>> Thank you for pointing this out. We have clarified in the manuscript that the purpose of the subsequent study is not to establish the already well-known relationship between WASH factors and U5 mortality and morbidity, but to co-produce slum upgrading and behavioural change interventions which can address these factors (among others) most effectively in the chosen locale.
Similarly, what do you hope to achieve or intervene with whatever information you may pick up? You have no substantive mention of intervention in your script save for a mention at the end around "co-development of integrated interventions to improve the slum-built environment & WASH alongside better animal husbandry and preventive practices to reduce the U5 infection". I am not sure why this cannot already be done with current data and what more information you need to know to help local NGOs (which on your website is your target medium for intervention) achieve this. What's missing, essentially, is why you need the new data you are hoping to find, and then what can realistically be done that is different and could not be done, or done as well, with current data. I think your piece reads so strongly like a preliminary and quick-scan study, it does not explain or justify the definitive need for such a study, or what potential benefit it may have in discrete terms. >>>> Thank you. We have clarified the presence of an intervention gap for interventions which use a One Health approach to co-design such interventions by working with policymakers and community members in this context. We have also expanded the discussion of how the findings of this feasibility study will inform the methodology of our subsequent study which addresses this intervention gap, as well as how it will inform health research in slum contexts generally.
2: The second major point is around your data and results. You have a very small N number, which is 25. This is outright far too small to publish as a discrete and useful data set. You are not able to present this as reliable or useful primary data, and you certainly cannot draw any conclusion from this. This does practically make your results section, and much of your discussion, unfortunately nullified. You can't attempt any correlations and you can't compare your data with other studies as you have done. >>>> We have realigned the focus of the paper and clarified that we do not aim to establish causal relationships to identify determinants of U5 infections due to the small sample size.
However, we are able to inform the methodology of future research in slum contexts, to characterise the chosen locale and to identify variables of interest for our subsequent study.
Equally important are the questions and presentation of questions and data you've supplied. This is really very unclear. First, the bulk of your data given in Table 1 is of households overall and not the U5s. This would be fine, if then the U5 divided data was presented, which it is not. You have two tables on household (=15) and then total people (=85) data but your single table on actual U5s primarily around feeding is first of all not attempted to be correlated with anything, and second of all not even discussed. I'm not sure what's happened there, but it makes it very difficult to then read paragraphs in results (e.g. " A strong…retrieve water"). It doesn't necessarily matter since the N number is probably too low to present anyway, but were you to re-write this section I would want a much clearer and more precise presentation of particular data around the U5s and what data sets you are able to aim to correlate, which is entirely missing. In both the n-number and data tables presented, you are unable to attempt any analysis.
>>>> Thank you, we have now presented the data on U5s in tables 3.1 to 3.3. We have presented the data collected more comprehensively, and explained how the data presented will be used to inform the methodology of future research From a medical point of view, I would have concern over your exploration of health and illness. In your introduction you highlight respiratory and gastrointestinal infectious diseases as predominant burdens of diseases and emphasise this. I do not see any detailed assessment of illness in your data gathering or illness. You are very vague when it comes to symptoms and illness, and the sole phrases used are: "evidence of infection / cough / fever".
This really does need more qualification. I don't know of anyone under 5 who doesn't cough, and while fever is relevant, you are not going to fund and execute a high-end longitudinal cohort study where your most central data point is only 'fever' in order to critically appraise and understand U5 illness. >>>> Thank you. We have clarified that future studies will focus on gastrointestinal and respiratory infections more specifically, by cross-referencing reports from multiple household members and by taking culture and culture-independent samples. We have clarified that this was beyond the scope of this feasibility study, and thus that this study relied on general measures of ill health (fever and cough), and we have explained the limits of such an approach. We have also clarified details of the survey method, including how 'fever' and 'cough' were defined to participants, and the limits posed by this method. 3: Similarly, and moving into the third major point which is around your conclusions and discussion, you have not presented data on several areas you try to draw conclusions from: vaccination status, nutritional status, distance from water, finance, etc. (Again, just to come back to the first point, and this is a run-through theme, what exactly are you trying to argue with such data -we know that vaccinations prevent certain infections, as does nutritional status, finance, etc.). The consequence of all of this is that when you do state in your discussion something similar to "Treatment seeking behaviour was primarily from private facilities with low vaccination compliance. This reflects the marked dependence of slum dwellers on the private health system and the intrinsic weakness of the public health care system in promoting immunization awareness." it becomes very hard to appreciate the point and justification. The crux here is that if you want to argue something, you are necessarily going to have to dive into a far more full critical analysis of the public/private availability and outreach of care in these settings. Further, once you have done that and once again, what is your proposed intervention and change based on your results? Again if the point of this whole study is just to more strongly argue for the need for public provision of vaccination, I'm not sure that justifies the study.
>>>> Thank you for this point. We have removed the italicised quote, have presented a greater range of results, and have ensured that we do not make any claims in our conclusion that are not supported by data explicitly presented in our results section. We have clarified that the purpose of the paper is not to determine the relationship between childhood illness and known risk and protective factors (vaccination, income, WASH, etc.), rather to scan for a) anomalous results which may merit further investigation in future research and b) methodological flaws which should be refined in subsequent studies Your next discussion point is: Future consortium studies involving culture and culture independent sampling to identify pathogens in the presence of infection symptoms will address this limitation. I'm not sure what this exactly is meant to mean, but it sounds like the future project intends to base diagnosis on microbiological lab results. This is obviously far better than the current survey methodology I've already critiqued, but I would question it's reasonability. It's entirely for you to decide whether or not it's possible, and if it is then that's very strong, but first of all I'm not sure of the widespread availability and accuracy of broad microbiological testing, and also you will very likely miss out many substantial respiratory and GI infections that do not end up growing anything in culture.
>>>> Thank you, we have included a discussion on the potential limits of using culture and culture-independent sampling that you have mentioned here 4: There are several other more minor points (inclusion of AMR, choice and analysis of survey questions) but I think I will just leave for now because that's quite a lot. I'm mindful this does sound like asking for an entire revamp of this paper, and while that is what I think is needed, there is significant potential here. If there is a genuine need for such a longitudinal study in this setting then I think that's fantastic and the basis of a genuinely excellent paper.
If you take away all the primary data, which really doesn't do very much, and instead focus on the critical literature appraisal of U5 morbidity and mortality in slum settings, that's something that would be very worthwhile to read. Your consortium is clearly investing a great deal of time, effort and money into this, so there must be a solid idea of what is missing in the world of child health. >>>> Thank you. We have expanded our literature review and have revamped the paper by pivoting the focus entirely away from causal inference and towards: literature review, identification of variables of interest for future studies, and informing the methodology used for research in slum contexts. Regarding AMR, we have also clarified in our discussion that future studies will survey participants' antibiotic use history, but that this was beyond the scope of this study. >>>> Thank you. We have elaborated in the first section about how WASH and nutrition interventions alone have often failed to produce transformative results in slum contexts, and have outlined the relevance of built environment, animal and ecosystem factors in child health in slum contexts. We have identified an intervention gap for using a One Health approach to co-produce interventions with policymakers and community stakeholders in slum contexts, and have reaffirmed the role of this preliminary study in informing the scope and methodology of such interventions, both by our consortium and by practitioners and researchers generally.
In short, switch this from a preliminary study that presents un-useful data into a sweeping critical appraisal that qualitatively justifies a future longitudinal study with proposed methodology. I think that would be a very interesting piece to read and a far stronger basis for your study than what you have currently.

Comments from Priyanie Amerasinghe
This study looks at utilising the One Health approach to understand the infection burden and associated risk factors in under 5 children living in Jaipur's urban slums.
As stated, the objectives of the research are twofold. They are, 1) To assess the feasibility of undertaking the above activities in a slum setting in India.
2) To identify preliminary risk factors and variables of interest for infections in children under 5 in slum environments.
Abstract: given in four separate paragraphs, is a summary of that has been described in the detailed text.

Introduction:
This section summarises the " One Health" approach and why it might give a better outcome in understanding the infectious diseases in slum settings than randomized control studies. It showcases the relevant global (including Indian) references in support of the hypothesis.
What was missing in this section was an overview description of Jaipur's slum setting/environment. Understanding the physical environment is an important component of a " One Health" . Slums in India are varied, environmental settings can be different too, therefore, capturing the heterogeneity across the slums is vital (notified and non-notified slums etc.). Because the authors refer to the study as a "feasibility study" undertaken prior to a larger study, capturing the nature of the external environment should have been a key component of the study, to understand the risk factors of under 5 children.
>>>> Thank you for this point. In the introduction, we have expanded the discussion of the nature of slum environments, with specific focus on India and Jaipur in particular, as relevant to the One Health approach and to this study. In the discussion, we have also spoken at greater length about the nature of Jaipur's urban slums from the results of the study, and how these characteristics should inform future research.

Methods:
Household survey : The household survey used in the study appears to be a standard one, used by many. Having a grassroots organization supporting the studies together with a Hindi speaking team for enumeration, is a plus point. However, self-reporting of illnesses can be problematic, unless traced for accuracy. A 30-day recall period for illness reporting can be too long, especially in settings where the daily household dynamics are a continuous struggle. Further, slums have a large moving population, therefore, attribution can be difficult and confounding too. A more nuanced understanding of health seeking behaviour may be required to collect health data that are reliable. There is a gamut of issues that are considered under the " One Health" approach, however, the different disciplinary and sectoral involvement is not discussed, although some questions are included in the questionnaire itself.
>>>> Thank you for this point. We have expanded upon the limitations of self-reporting of symptoms in the discussion, and have presented more results from survey questions which cover the broader range of issues. We have also highlighted the need for future research to address further issues, including a broader sectoral and disciplinary involvement and antibiotic use history. We have also added to the discussion the need to consider slums' moving populations, and the resulting difficulty in attribution.
Sampling : This has been carried out in 6 slums found in 3 areas, with the support of a charitable organization. Slum populations are large, therefore, the number sampled (n=15) for a feasibility study appears to be too small. The characteristics of slums can be very different and one would have expected a feasibility study to capture such differences in a " One Health" approach.
>>>> Thank you for highlighting this. We have expanded the discussion of the limits posed by our sample size, and have presented more results which cover a range of One Health factors which were not presented in the first draft of the manuscript. We have clarified that we do not aim to infer causality about infection determinants from this small sample; rather to inform the methodology of future research and to identify variables of interest.

Results:
Purposive sampling can be accepted, however, given the small number sampled, in a heterogeneous setting, the " One Health " approach is compromised. In terms of health seeking behaviour, especially within India, one has to describe what "private consultation" means. It can vary from a private medical doctor to a wise man/woman in the community.
Moving populations are a continuous source of infections and children's external physical environment can confound it. Exposure to animals is not discussed at all. >>>> Thank you for this point. We have discussed the interaction between small sample size and purposive sampling. We have elaborated our discussion of exposure to animals in the introduction. In the conclusion, we have discussed exposure to pests. We have also highlighted that exposure to companion and livestock animals could not be discussed because only one household reported owning one -we have discussed that this could represent a misunderstanding about the definition of companion and livestock animals, and highlighted the need for researchers to measure the presence of such animals directly where possible.

Discussion:
In this section, the results from questionnaire are discussed. The authors also highlight the need to consider the " One Health " approach as part of future studies, however, the title states otherwise -that a " One Health " approach is being used. There is a contradiction here.
One health approach has been around for a while and it discusses how multiple disciplines and sectors should look into integrated solutions for health problems. It is said that professionals of human and animal health, environment, law enforcement, policy makers should look for solutions together with communities that are affected. If this study had explored these key issues as part of their study, together with a larger sample size, it could have been considered for publication. However, in its present form, it is not suitable for publication, in this Journal, UCL Open: Environment.
>>>> Thank you for bringing this up. We have reclarified this in the introduction and discussion. The authors highlight the need for a One Health approach to be used in future interventions in this locale: this preliminary study is informed by the One Health ethos, and investigates the feasibility of using this approach for a subsequent full-sized study.

Comments from Carla-Leanne Washbourne
Thank you for your submission to UCL Open: Environment. As Handling Editor, I recommend that you revise your paper according to the reviewers' comments.
>>>> Thank you for your insights, we have incorporated your comments throughout the paper.
Please take into particular consideration: • Clearly justifying the need, context and proposed interventions of this preliminary effort and the full study and the new information that it is intended to add to the existing evidence on the relationship between WASH and U5 mortality and morbidity.
>>>> Thank you for this comment. We have clarified that the purpose of the study is not to add to the substantial existing evidence regarding the relationship between WASH factors and U5 mortality and morbidity, but to inform the focus and methodology of future studies which co-produce interventions to address WASH factors alongside a range of One Health infection pathways. We have elaborated on the intervention gap that would be addressed by a subsequent full-sized study • Articulating the nature of the 'One Health' framing. As Reviewer 2 (Priyanie Amerasinghe) notes: "you highlight the need to consider the " One Health " approach as part of future studies, however, the title states otherwise -that a " One Health " approach is being used." >>>> Thank you for drawing attention to this issue. We have clarified this in the introduction and discussion. The authors highlight the need for a One Health approach to be used in future interventions in this locale: this preliminary study is informed by the One Health ethos, and investigates the feasibility of continuing to use this approach for a subsequent full-sized study.
• Considering the level of completeness of this article for publication at this time, in this format. The presented study has a small N number and is therefore limited as a standalone dataset.
>>>> We agree fully with this comment and have clarified that the purpose of the study is not to make causal inference about U5 infection determinants using this small dataset, but instead to inform the methodology and focus of future research in slum settings generally, as well as for our subsequent study.
• Revisiting data presentation, particularly considering / justifying the framing of 'health and illness'. Reviewer 1 (Mustafa Abbas) in particular comments that the current manuscript is: "vague when it comes to symptoms and illness, and the sole phrases used are: "evidence of infection / cough / fever". This really does need more qualification." >>>> Thank you for raising this -we have clarified how symptoms were defined to participants, and how distinct episodes of illness were defined • Ensuring that data is included for all areas covered within the discussion and conclusions and provide fuller evidence of critical engagement with the literature, particularly that of integrated solutions for health problems within the 'One Health' approach >>>> Thank you for pointing this out. We have expanded the results section to include a full presentation of data on a range of One Health factors, and have expanded our literature review section to include a more explicit discussion of the relevance of One Health to U5 morbidity and mortality in slum settings: generally, in India and in Jaipur specifically

Comments from Shubhagato Dasgupta
Thank you very much for your submission to UCL Open Environment. It was indeed an interesting paper and I have considered your approach, analysis and discussion. I agree with the comments made by Mustafa Abbas . In my view the main issues in this paper are the following: >>>> Thank you for your comments. We have made every effort to incorporate them in order to improve the paper • The relation between this Rapid Household survey and the prospective cohort studies by the Childhood Infection and Pollution (CHIP) Consortium is not clear. What aspects of feasibility is this study testing? What lessons does it have for the cohort study? A clearer answer to these questions will make the paper more focused.
>>>> Thank you for mentioning this. In the introduction, we have clarified the ways in which this study aims to inform the future cohort study. In the discussion, we have elaborated on the specific take-aways of this study, and how these will be used to inform the methodology of the future study • The sample size of 25 HHs is very small, also given the fact that the slum population of Jaipur is close to 150,000 HHs. Drawing results from such a small and also purposive quantitative sample could be misleading.
>>>> Thank you. We have clarified that the purpose of the study is not to draw causal inference about the determinants of U5 infections, but to identify areas of interest for, and to inform the methodology of, future studies including that of our consortium. We have also made more explicit the discussion of the limits of our sample size and sampling method • Furthermore the results seem to suggest that a One Health approach may not be a good hypothesis as much of the correlation is with water and sanitation (well established facts), and the contribution of the presence of animals in the household seems weak! How does this impact the feasibility of the prospective cohort study.
>>>> Thank you for this. We have elaborated on the prevalence of pests. We have also highlighted that misunderstandings between the participants and researchers may have hindered our ability to collect information about livestock and companion animals, and detailed how future study may overcome this to gain a better understanding of One Health infection pathways. We have noted the apparent importance of WASH factors, and have discussed how subsequent interventions will aim to co-design behavioural change and slum upgrading interventions which target them • I also agree that the Tables in the results section present data that is not important for the discussion as pointed out by Mustafa Abbas .
>>>> Thank you. We have expanded our presentation of results, and have made more explicit reference to them in the discussion • A stronger focus on what lessons this Rapid Survey presents for the feasibility of the larger cohort study based on One Health approach, with a cursory discussion on the results per se will go a long way in strengthening this paper >>>> Thank you for this. We have considerably expanded our discussion of how this study can inform the focus and methodology of the future cohort study, and have realigned the paper to make these take-aways one of the key focuses of the paper To whom it may concern, Follow receipt of reviews on the first draft of the manuscript, we have worked to incorporate all comments made on the paper. The changes made are detailed here: -The reviewers correctly pointed out ambiguity regarding the nature of the study, and as such the principal change has been to clarify the purpose of the paper. We reaffirm that, due to the nature of the feasibility study and the small sample size, the purpose of the investigation is not to make statistically significant causal inference about the determinants of childhood infections, but instead to characterise the target community, to determine variables of interest, and to inform the methodology used by our consortium's subsequent research and by researchers generally. The language used throughout the paper has been altered accordingly -Following the request of some reviewers, we have reported our results in greater detail -Following the comment of one reviewer, we have included a more detailed literature review in order to reaffirm the need for this study to take place and to identify an intervention gap -Reviewers noted a number of limitations to the study. We have expanded our discussion of the study's limits, and have been sure to include the points raised by the reviewers -In the discussion, we have outlined more explicitly and in greater depth how the results of this study will inform the methodology used in future research in slum settings Best regards, The CHIP Consortium ____________________________________________________________________________ To whom it may concern, The paper under review, Assessing the infection burden and associated risk factors in children under 5 across Jaipur's urban slums: A feasibility study using a One Health approach, presents findings from a formative feasibility study which will inform future research activities for a much larger research project which will be undertaken by the Childhood Infections and Pollution (CHIP) Consortium.
This project (called the CHIP project) will aim to identify risk factors and infection pathways for children under 5 in slums in India, Indonesia, and Chile. The CHIP project will employ a One Health approach to identify infection pathways through biological sampling, observational research, cross-sectional surveys, analysis of routinely collected data, and interviews with community members and stakeholders.
The aims of this formative research were: 1) To assess the feasibility of undertaking the above activities in a slum setting in India 2) To highlight any issues with the data collection method employed, and to identify how this method could be refined in future studies, both by the CHIP consortium and by researchers in general 3) To identify preliminary variables of interest for infections in children under 5 in slum environments 4) To detect any surprising or anomalous apparent relationships which merit further study in subsequent research Prior to COVID-19, data collection activities had begun to take place in Jaipur. Feasibility studies have also been undertaken in Indonesia and Chile.
Best Regards, The CHIP Consortium ____________________________________________________________________________ To whom it may concern, All co-authors contributed to the design and implementation of the study, analysis and interpretation of the data, and the drafting of the report. The CHIP Consortium co-investigators had the opportunity to critically review the results and to contribute to the process of finalising the report. The co-authors vouch for the accuracy and integrity of the work, and accept full responsibility for the content of the paper. Co-authors declare no competing interests. This study was jointly funded by the University College London Grand Challenges 2018-19 programme and Aceso Global Health Consultants Limited.
Best regards, The CHIP Consortium co-investigators

Abstract
Purpose: Infectious diseases are one of the leading causes of death among children under five (U5s) both in India and globally. This is worse in slum environments with poor access to water, sanitation and hygiene (WASH), good nutrition and a safe built environment.
Globally, a One Health (i.e. human, animal and environment) approach is increasingly advocated for by the WHO-FAO-OIE tripartite to reduce infections and antimicrobial resistance. As under-5s living in peri-urban slums are exposed to household-and communityowned companion and livestock animals and pests, the CHIP consortium hypothesised that employing a One Health approach to co-produce behavioural change and slum upgrading interventions may reduce this burden where other WASH and nutrition interventions have failed.
This study aimed to assess the feasibility of employing a One Health approach to assess under-5 infection and risk factor prevalence in Jaipur's peri-urban slums, prior to undertaking prospective cohort studies involving culture and culture-independent sampling of under-5s and animals across our study sites in Jaipur (Rajasthan, India), Jakarta (Indonesia) and Antofagasta (Chile).

Methods:
We administered a rapid household survey to 25 purposively selected households across six slums in Jaipur. The questionnaire used evaluated infection prevalence, healthseeking behaviours, the built environment, the presence of companion and livestock animals and pests, and individual-and household-level demographics. We displayed the correlations between infection incidence and a range of factors in our sample, and displayed the portion of children under 5 who experienced one or multiple episodes of ill health, categorised by a range of One Health factors.
Results: Parents reported at least one recent episode of ill health for a large portion (40%) of under-5s within the last 30 days. 80% of under-5s had no access to safe drinking water; every household reported the presence of at least one kind of pest within the respondent's own home; and 20% of under-5s' feeding equipment was cleaned with water only. Only one household reported owning a companion or livestock animal, potentially reflecting confusion about the definition of these animals. The incidence of infection appeared to be related to WASH and socio-economic factors as expected.

Introduction
Infectious diseases, particularly respiratory and diarrhoeal diseases, have been the leading cause of child mortality over the past two decades [1]. Home to 20% of the world's children, India is the largest contributor to global mortality in children under the age of five (U5s) and is among the top ten countries contributing to the global childhood infection burden [2]. In terms of disability adjusted life years (DALYs), diarrhoeal and respiratory infections are also two of the five leading causes of ill health in children [3]. Additionally, child and maternal nutrition and air pollution levels were also identified as leading risk factors for DALYs in 2016 [3].
India is one of the largest consumers of antibiotics globally, propagating the spread of emerging antimicrobial resistance (AMR) [9]. The threat of AMR is attributed to a set of factors which includes poor public health infrastructure, rising incomes, a high disease burden and undernutrition [10]. The emergence of AMR is compounded by low-cost unregulated antibiotic sales [11] and high rates of antibiotic prescription, with antibiotics prescribed to roughly 30% of all patients seeking care [12][13] [14]. Diagnostic uncertainty, patient expectations of receiving antibiotics, practice sustainability, influence from pharmaceutical company representatives and inadequate knowledge are factors influencing physicians' prescribing practices [15]. The Red Line Campaign has been launched to curb over-the-counter antibiotic use in India [11]: however, systemic challenges in public health care delivery, such as low immunisation rates [17][18], continue to contribute to the burden of drug-resistant infections [11].
India has also seen rapid, often unorganised urbanisation in the last few decades, resulting in an increase in the population of peri-urban slum dwellers [32]. Jaipur is no exception, and the urban slum-dwelling population there has swelled in recent years to 415,000 people, or 13% of the city's population. Despite their potential role in value creation, they are chronically excluded from the formal economy and face systematic under-provision of public services [36]. This trend has worsened the risk of poor housing conditions, overcrowding, a lack of potable drinking water and access to sanitation facilities, poor hygiene practices, poor nutrition and incomplete immunisation [26] [28] [33]. The overcrowding and substandard housing prevalent in slum environments can worsen the risk of fever, chills and acute respiratory and gastrointestinal symptoms; the poverty faced by slum-dwellers worsens the risk of childhood diarrhoea and infection; and unemployment and lack of education increase the risk of infection and restrict access to healthcare services [24] [25] [30] [31]. In addition, it is often difficult to quantify the incidence of childhood diseases and malnutrition in high-density informal settlements [32]. For these reasons, the poorest residents of urban and peri-urban settlements may be at greater risk of under-5 mortality than rural children [35] [36].
Childhood infections are widespread in Indian slums, with a reported annual prevalence of 8% and 8.5% for diarrhoeal and respiratory infections, respectively [4]. Globally, children under 2 account for 80% of pneumonia deaths and 70% of deaths from diarrhoea [34]. Access to safe water, sanitation, and hygiene (WASH), nutrition and the built environment are important infection determinants, especially in slum areas [5]. Whilst country-led programmatic efforts to improve WASH have included toilet construction, better solid waste management, and raising awareness through the Swachh Bharat Mission (the urban component of India's flagship programme), implementation issues are evident [8].
Zoonotic infections represent as much as 60% of all known infections and 75% of emerging infectious pathogens [6]. Slum dwellers come into frequent close contact with animals (including pests, livestock and companion animals), increasing the risk of diarrhoea via faecal contamination [28]. This has led to the recommendation of using a One Health approach by the tripartite WHO-FAO-OIE tripartite to address infections and AMR [19].
With mixed results from randomized controlled trials of WASH and nutrition interventions, and given the clear role of built environment, ecosystem and animal factors in determining childhood morbidity in urban slums, the Childhood Infection and Pollution (CHIP) Consortium hypothesized that utilizing a One Health approach to co-develop behavioural change and slumupgrading interventions may work to reduce the infection and AMR burden in U5s in urban slums. Although the One Health approach is increasingly well-recognised, there are few examples of co-developing One Health interventions with slum-dwellers and policymakersthis represents an important intervention gap, with considerable evidence reaffirming the potential efficacy of such interventions.
In advance of prospective cohort studies across Jaipur (India), Jakarta (Indonesia) & Antofagasta (Chile) involving culture and novel culture independent (i.e. metagenomic) sampling of U5s, caregivers, pests, and companion and livestock animals, we aimed to assess the feasibility of utilizing a One Health approach to assess infection and risk factor prevalence in U5s in Jaipur's urban slums.
The purpose of this study is not to infer statistically significant causality about the determinants of childhood infections, given the limited sample size (exacerbated by purposive sampling). Rather, it aims to highlight an existing intervention gap, and to investigate the feasibility of further research to fill this gap in the context of Jaipur's peri-urban slum communities. By conducting this study, we also aim to identify any shortcomings of the data collection method employed, and to scan for anomalous results that merit further investigation in subsequent study. We also collected considerable amounts of information about the individual-level and household-level characteristics of participants, which will deepen our understanding of the demographic and socio-economic makeup of the target community, permitting more culturally tailored future interventions. This will allow for more feasible and acceptable study design both in future research by our consortium and for those conducting research in slum communities generally.
While we have highlighted the importance of AMR and gastrointestinal and respiratory infections, measuring these directly is beyond the scope of this preliminary study, and we instead relied on general measures of ill health (caregiver-reported incidence of fever and cough).

Household Survey
We developed a household-survey to capture information on participants' demographics, health behaviours, illness history, and care-seeking practices. The survey was developed by adapting questions from the WHO Household Survey for Medicine Use [21] with other surveys previously utilized by our team [20], and then adding questions to explore human-animal interactions from a One Health perspective. All questionnaires were translated into Hindi text and delivered by a native Hindi speaking facilitator to establish the appropriateness of the questions as well as their cultural and contextual validity. Appendix 1 contains a full copy of the questionnaire in English. The Hindi version can be requested through email to the study authors.
The survey was delivered with the assistance of Hindi speaking facilitators from a local charity, Jeevan Ashram Sanstha (JAS), which has experience working with and engaging slum dwellers in local projects. All JAS facilitators were proficient in both Hindi and English and were able to deliver the survey questions in Hindi, while simultaneously relaying data to be recorded in English by a field researcher (MAC).

Sampling
We selected three localities in Jaipur (Jal Mahal, Shastri Nagar and Vidhyadhar Nagar) within the JAS network (Figure 1), and selected households with a known child U5 across six individual slums for interviews in October 2018. Sample households were selected purposively by door-to-door visits to inquire if a U5 child was resident at the household. The heads of households (as defined by dwellers) with an U5 child were invited to participate in an interview. All interviews were conducted within or just outside of the participant's home. At the start of each interview, the aims of the study were explained (verbally, in Hindi), and consent was obtained for each participant. Where the participant was unable to sign their consent, a thumb impression was taken instead.

Analysis
Association was calculated using correlation to show strength of significance between certain key variables. As this was a feasibility study with no power calculations done a-priori, significance was not tested for. Correlations were calculated for key variables using the corr command in R version 4.0.2.

Participant Demographics
In total, 15 household were sampled with 85 individual household members recorded. Of these 85 individuals, 25 were U5 children. The surveys were delivered across four days (October 12th 2018, October 17 th 2018, October 21st 2018, October 25th 2018) over a span of two weeks. In many cases, survey facilitators had worked in the slum areas before and were aware of which households had residents with young children, resulting in these households being preferentially selected. Likely due to this, 100% of households which were approached agreed to participate.

Children Under Five Years of Age
Cases of infection were categorised as distinct episodes, where the first episode was recorded as the head of household recalling a child's case of illness according to its symptoms or the need for care seeking. Cough and fever were classified as being an acute episode, appearing suddenly in a previously healthy child. Illness in the past 30 days was recorded first as an episode 1 illness. If the illness did not subside after care seeking, or reemerged after care seeking, a second episode of the illness was logged, and so on.
Of all 25 children within the households surveyed, evidence of infection was found in 40%. The reported symptom for 70% of episode 1 illnesses was cough, while fever accounted for the remaining 30%. 55% (6/11) of childhood illness bouts were reported to have subsided after care (episode 1) within the past 30 days, while a further 45% (5/11) of children had either developed an illness which did not subside or developed two illnesses (episode 2) within the past 30 days.

Correlation Analysis
A correlation analysis was run among a number of variables ( figure 2). This provides a methodological template for assessing the relationship between childhood infections and One Health factors in a full-sized study. Although our sample size precludes statistically significant causal inference, this exercise allows us to see if variables generally behave as expected. Instances where this is not the case could be indicative of statistical noise, but also of potential mismeasurement or an unexpected relationship which should be investigated in further study.
Our variables of interest generally behaved as expected. Sharing toilet facilities was positively correlated with episodes of illness (ρ = 0.62), and monthly household expenditure was negatively correlated with episodes of illness (ρ = -0.45). Illness episodes also had a negative correlation with age (ρ = -0.22), the amount of vitamin supplements given (ρ = -0.22) and the number of hepatitis vaccinations (ρ = -0.15). A number of variables which we would expect to be related to childhood illnesses showed negligible correlation (relative size of child, distance walked to collect water, total number of vaccinations). No variables displayed a strong correlation with the incidence of childhood infection in the opposite direction from what was anticipated.

Discussion and Conclusions
The observed characteristics of our sample help to outline lessons for subsequent study. 80% of under-5s (20/25) lived in households without access to safe drinking water, which should be a focus of future slum upgrading and built environment interventions in these locales. Only one household reported owning an animalgiven the known prevalence of companion and livestock animals in slum environments [28], this is surprising and could represent a misunderstanding or miscommunication when talking about companion and livestock animals. This meant that, although exposure to domestic animals is a core component of One Health, we were unable to discuss it in depth in this paper. In subsequent studies, researchers will directly observe the presence of animals in households where possible, to overcome this potential limitation. Similarly, no parents reported that their U5 child was large relative to other children: while it is possible that we simply selected a sample with small-to-average children, this may also reflect inaccurate parental perceptions of children's size, and future research should rely on direct measurement of U5 children instead.
Pests, including rats and flies, were highly prevalent and every household in our sample reported the presence of at least one kind of pest. Future interventions must therefore identify ways to reduce the prevalence of these potential disease vectors. 20% of under-5s' feeding equipment was cleaned using water only. This, too, represents a pertinent target for future low-cost behavioural change interventions.
At least one incidence of illness was reported in the last 30 days for 40% of under-5s in our sample, which is considerably higher than the childhood infection incidence reported in previous research [4]. This brings attention to the limitations of parental reporting of symptoms. To overcome this, future studies may a) ask multiple family members for their perceptions of children's recent illness and cross-reference or b) take culture and cultureindependent samples to identify the presence of pathogens. Sampling would also allow us to assess the ecology of resistant bacteria in the human-animal-environment interface. Because the availability of accurate, low-cost culture and culture-independent sampling tests may be limited, and because metagenomic sampling may overlook some infections which do not grow anything in culture, a combination of a and b could be employed in subsequent research.
A number of other limitations presented themselves. For one, our small sample size may have been exacerbated by purposive sampling: in future study we will employ random sampling and use a large sample size which permits statistically significant causal inference, with power calculations done a priori. However, even for the purposes of this preliminary study our small sample size may be a concern. In a full-sized study, we will address respiratory and gastrointestinal infections directly, rather than relying on general measures of ill health (fever and cough).
We must also be cognisant that the mobility of slum populations can create difficulty in attributing the causes of infection and ill health. To mitigate this concern, subsequent research will take into account slum-wide built environment factors in addition to those at the household level, and will gather data about participants' movement patterns. Although it was beyond the scope of this feasibility study, future research should expand in scope to include a wider range of disciplinary and sectoral involvement in order to take full account of One Health considerations. This will encompass engagement with policymakers and community leaders, and experts from the fields of veterinary science, social sciences and ecology. Finally, future study will gather data on participants' use of antibiotics in order to better understand the role of AMR.
We found no evidence to contravene the commonly understood relationship between childhood illness episodes, sanitation access and socioeconomic status [8] [22]. Thus, subsequent studies in this locale will not focus on the extent to which WASH and income determinants are protective of infection, but instead on co-designing behavioural change and slum upgrading interventions which are most likely to address these determinants (along with a range of One Health determinants) effectively.
Once these limitations are addressed, future formative studies will enable the identification of One Health infection pathways to be interrupted with the co-development of integrated interventions to improve the slum built environment and WASH factors alongside better animal husbandry and preventative practices to reduce the under-5 infection and AMR burden in targeted slums.

Contributions and Acknowledgements:
All co-authors contributed to the design and implementation of the study, analysis and interpretation of the data, and drafting of the report. The CHIP Consortium Co-Investigators had the opportunity to critically review results and to contribute to the process of finalising the report. The co-authors vouch the accuracy and integrity of the work, and accept full responsibility for the content of the paper.

Funding:
This study was jointly funded by the University College London Grand Challenges 2018-19 programme & Aceso Global Health Consultants Limited

Declarations of Interest:
Co-authors declare no competing interests.

Research:
This study included research on human participants, who were given free, prior and informed consent.

Consent
Namaste. My name is _________________________________. I am working with Save the Children, Rajasthan. We are conducting a survey on health behaviours, care seeking and infection rates in children under five years of age. The information on family welfare and infection rates that we collect from households and individuals will help us to develop a larger study to improve health outcomes in children. Your household was selected for the survey. I would like to ask you some questions about your household. The questions usually take about 60 minutes. All of the answers you give will be confidential and will not be shared with anyone other than members of our survey team. Your participation in the survey is voluntary. If I ask you any question you don't want to answer, just let me know and I will go on to the next question or you can stop the interview at any time. *Generally speaking, persons who are present in the household and eat food cooked in the same kitchen during the last one month or who are known to be usual residents of the household and have stayed there for part of the past one month. Those who are not present at the time of visit of the enumerator but are expected to return in a month are treated as 'usual members'.

SECTION 3: HOUSEHOLD SOCIO-ECOMONIC STATUS
Now I will ask you some information about you and your family's education and demographics.