Cross-sectional study of the association of social relationship resources with Staphylococcus aureus colonization in naturally occurring social groups along the US/Mexico border

Steven D Barger; Monica R Lininger; Robert T Trotter, II; Mimi Mbegbu; Shari Kyman; Kara Tucker-Morgan; Colin Wood; Briana Coyne; Benjamin Russakoff; Kathya Ceniceros; Cristina Padilla; Sara Maltinsky; Talima Pearson

doi:10.1371/journal.pone.0284400

. 2023 Apr 13;18(4):e0284400. doi: 10.1371/journal.pone.0284400

Cross-sectional study of the association of social relationship resources with Staphylococcus aureus colonization in naturally occurring social groups along the US/Mexico border

Steven D Barger ^1,^*, Monica R Lininger ², Robert T Trotter II ^3,⁴, Mimi Mbegbu ⁵, Shari Kyman ⁵, Kara Tucker-Morgan ⁶, Colin Wood ⁵, Briana Coyne ⁵, Benjamin Russakoff ⁵, Kathya Ceniceros ⁶, Cristina Padilla ⁶, Sara Maltinsky ⁵, Talima Pearson ^3,^5,^*

Editor: Samiullah Khan⁷

¹Department of Psychological Sciences, Northern Arizona University, Flagstaff, AZ, United States of America

²Department of Physical Therapy and Athletic Training, Northern Arizona University, Flagstaff, AZ, United States of America

³Center for Health Equity Research, Northern Arizona University, Flagstaff, AZ, United States of America

⁴Department of Anthropology, Northern Arizona University, Flagstaff, AZ, United States of America

⁵Pathogen & Microbiome Institute, Northern Arizona University, Flagstaff, AZ, United States of America

⁶Northern Arizona University, Yuma, Arizona, United States of America

⁷The University of Lahore, PAKISTAN

Competing Interests: The authors have declared that no competing interests exist.

^✉

* E-mail: talima.pearson@nau.edu (TP); steven.barger@nau.edu (SDB)

Roles

Steven D Barger: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Validation, Writing – original draft

Monica R Lininger: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Validation, Writing – original draft

Robert T Trotter II: Conceptualization, Formal analysis, Funding acquisition, Methodology, Project administration, Validation, Writing – review & editing

Mimi Mbegbu: Data curation, Investigation, Methodology, Project administration, Supervision, Writing – review & editing

Shari Kyman: Data curation, Investigation, Methodology, Project administration, Supervision, Writing – review & editing

Kara Tucker-Morgan: Data curation, Investigation, Project administration, Supervision, Writing – review & editing

Colin Wood: Data curation, Investigation, Methodology, Writing – review & editing

Briana Coyne: Data curation, Investigation, Methodology, Writing – review & editing

Benjamin Russakoff: Investigation, Writing – review & editing

Kathya Ceniceros: Investigation, Writing – review & editing

Cristina Padilla: Investigation, Writing – review & editing

Sara Maltinsky: Data curation, Investigation, Project administration, Supervision, Writing – review & editing

Talima Pearson: Conceptualization, Data curation, Funding acquisition, Investigation, Methodology, Project administration, Supervision, Validation, Writing – original draft

Samiullah Khan: Editor

PMCID: PMC10101449 PMID: 37053196

Abstract

Asymptomatic carriage of Staphylococcus aureus is a major risk factor for subsequent clinical infection. Diminishing returns from mitigation efforts emphasize the need to better understand colonization, spread, and transmission of this opportunistic pathogen. While contact with other people presents opportunities for pathogen exposure and transmission, diversity of social connections may be protective against pathogens such as the common cold. This study examined whether social relationship resources, including the amount and diversity of social contacts, are associated with S. aureus colonization. Participants were community members (N = 443; 68% Hispanic) in naturally occurring social groups in southwestern Arizona. Four types of social relationships and loneliness were assessed, and samples from the skin, nose and throat were obtained to ascertain S. aureus colonization. Overall S. aureus prevalence was 64.8%. Neither the amount nor the diversity of social contacts were associated with S. aureus colonization. The concurrent validity of the social relationship assessments was supported by their moderate intercorrelations and by their positive association with self-rated health. The results suggest that the association of social network diversity and susceptibility to the common cold does not extend to S. aureus colonization. Conversely, colonization prevalence was not higher among those with more social contacts. The latter pattern suggests that social transmission may be relatively infrequent or that more intimate forms of social interaction may drive transmission and colonization resulting in high community prevalence of S. aureus colonization. These data inform communicable disease control efforts.

Introduction

Social network diversity, denoted by the number of different social relationship roles in which one participates (i.e., spouse; parent; work; school; neighbor), presents opportunities for pathogen exposure and subsequent transmission. Conversely, social network diversity is associated with a lower probability of symptomatic infection after intentional exposure to cold viruses [1]. This suggests that social relationship resources may be protective for some infectious diseases. However, human exposure to, and illness from infectious agents, occurs in a complex ecological context that was intentionally excluded from infectious challenge paradigms because all study participants were exposed to the infectious agent [1, 2]. Importantly, this putative salutary link between social relationships and infectious diseases has only been explored with cold viruses and is based upon unplanned analyses from a single study. The potential importance of the association between social networks and communicable diseases warrants further evaluation as it is critical for mitigation.

The present study addresses gaps in our understanding of the links between social resources and infectious diseases by examining the association of social network diversity with colonization by Staphylococcus aureus in naturally occurring groups of community residents. S. aureus is a bacterium that many humans carry as a commensal, without infections. However, if these bacteria penetrate the outer layers of skin or mucosa, they act as a pathogen and can cause mild skin infections as well as dangerous invasive infections [3]. In 2017 S. aureus blood infections caused almost 20,000 deaths in the United States (U.S.) [4]. It is estimated that about a third of the U.S. population is colonized with S. aureus [5]. However, our recent work using a combination of culture-based and genomic assays shows a S. aureus prevalence of ~66% and suggests that previous prevalence reports are underestimates [6]. While hospital-onset and healthcare-associated invasive infections of methicillin-resistant S. aureus (MRSA) have decreased, community-associated MRSA and methicillin-susceptible S. aureus (MSSA) infections have not [4, 7]. The epidemiological importance of such a community-based reservoir of S. aureus underscores the importance of community sampling to understand prevalence, transmission, and drivers of colonization. Colonization is a major risk factor for infection, with genetic studies showing that colonizing strains of S. aureus, i.e., the strains found on skin, nares, etc., are commonly identical to infecting strains, suggesting that patients typically infect themselves [8–10]. Thus, S. aureus colonization provides a marker for an infectious disease that is both prevalent and closely tied to clinical infection. Importantly, when assessed in community settings, S. aureus colonization remains situated in, and therefore potentially influenced by, the social processes putatively underlying infectious disease exposure.

We examined several social relationship indicators linked to health in general and indicative of social interactions that may drive colonization. These included social network diversity and social network size (the number of people in the social network). Both network diversity and network size are considered measures of social integration, reflecting individual participation in a broad range of social relationships [11] (sometimes labeled social engagement [12]). We complemented these social network metrics with a social integration measure that is used in public health surveillance and only counts interaction with persons outside one’s household and disaggregates different forms of social interaction (i.e., phone versus in-person contacts). Importantly, this social integration measure robustly predicts hard health endpoints (i.e., mortality) in large population-based samples and is clearly distinct from socioeconomic status determinants of health [13, 14]. Thus, this social integration measure complements the other social network metrics and provides a bridge to existing population health surveillance.

In addition to these structural social relationship measures this study also assessed loneliness. Loneliness reflects subjective satisfaction with both the quality and quantity of one’s social relationships [15, 16]. Loneliness can therefore disentangle the relative importance of perceived social relationship deficits, which may or may not align with being socially isolated as indicated by quasi-objective social integration scores [15, 17].

Self-rated health was included as a convergent outcome for the analysis of social relationships and S. aureus colonization. Self-rated health, typically measured by asking respondents to rate their own health from poor to excellent, is a robust predictor of mortality [18–21] and captures health status beyond established clinical and biomedical assessments [21, 22]. Because self-rated health is positively associated with several measures of social integration [23, 24], including the public health version we use here [25], self-rated health was used as an additional health status outcome to confirm the convergent validity of the social relationship assessments.

Given the novelty of the outcome variable in relation to social relationship resources, no predictions were made regarding the association of social relationships with S. aureus colonization. Instead, several working hypotheses were specified [26]. First, if social network diversity is inversely associated with S. aureus colonization, this would extend the literature on salutary social relationships to an infectious agent other than common cold viruses. To the extent that colonization is also inversely associated with other social relationship resources, such as loneliness and/or network size, that would show that the social determinants of infectious disease susceptibility are more extensive than previously understood. If S. aureus colonization is unrelated to social network diversity specifically, and to other social relationships generally (i.e., loneliness), this would provide evidence for a boundary for salutary social relationship resources on infectious disease susceptibility. A competing prediction is that social contacts increase exposure to persons colonized with S. aureus. Therefore the number of contacts, as indicated by social network size, would be positively associated with S. aureus prevalence. Similarly, if colonization is unrelated to more frequent social contacts, it does not preclude the possibility that more intimate forms of social interaction (e.g., sexual relationships, cohabitation) may be more likely to result in transmission and colonization. Irrespective of these patterns it was expected that social networks and social integration would be positively associated with self-rated health [23–25].

Materials and methods

Study overview

This study is part of a larger investigation of determinants of S. aureus colonization and transmission in social groups recruited in south Yuma County in Arizona [6, 27, 28]. Briefly, research team members from the community were trained to recruit participants, to supervise collection of survey data and to supervise participants’ self-collected swabs for S. aureus culturing. Each participant received a gift card as an incentive. Year 1 was excluded from this analysis as the social network index was only assessed in years 2 and 3 (March 2019 to March 2020). All adult participants provided verbal informed consent to maintain participant anonymity. Consent was witnessed and documented by two staff members. The study (project 1116783) was approved by the Northern Arizona University Institutional Review Board, which also approved verbal rather than written informed consent.

Participants

Groups of two or more people who appeared to be together were invited by study staff to participate in the study. Study staff confirmed that those approached were part of a self-identified group. If they were not part of a self-identified group they were not invited to participate. No other health screening or eligibility restrictions were required. Children were eligible to participate but because their survey responses were often completed by adult proxy respondents, they were excluded and only adults were included. Thus analyses are restricted to adults 18 years and over (Fig 1). The analytic sample size was 443 (442 for self-rated health analyses) and is a subset of a previous study which included all age groups [6]. Race and ethnicity were self-reported by participants using prespecified categories [29].

Social relationship assessments

Social network index

The SNI [1] assesses relationships across 12 types of social roles; spouse/partner, child, in-laws, parents, other close family members, friends, neighbors, coworkers, school contexts, volunteer work, religious contexts, as well as a broad category representing nonreligious social/recreational/professional groups. The SNI also assesses the number of persons interacted with in each social role. If persons interacted (by phone or in person) at least once every two weeks they received a point for that social role domain and these points were summed to create the network diversity score (range 0–12). Network size (the total number of social contacts across those domains) was the sum of all persons with whom the respondent interacted in these roles. Network size counts were naturally limited for some social roles (e.g., 1 person for a spouse/partner role; 2 people each for parents and in-laws) but for other domains (e.g., close friends) response options ranged from zero to seven or more. The number of persons in the work domain ranged up to 14 as both the number of persons supervised (0–7+) and the number of nonsupervisory contacts (0–7+) were included in the sum (possible range 0–75). Social network diversity, but not network size, has been linked to infectious disease risk [1].

The last SNI question related to nonreligious group membership was modified from the original [1]. “Fitness classes” was added as an example group activity to make the examples more contemporary and to make the number of contacts assessment parallel to the relatives/close friends/religious group questions, i.e., top coded at 7 or more persons.

Social integration and loneliness

Social integration was measured using seven items from the 2001 US National Health Interview Survey (NHIS) [30]. These items capture social contacts with persons not living with the respondent. Questions referenced interactions in the past two weeks and included in-person or phone contact with friends or family, participating in a group social activity, attending a religious service, and eating out. The eating out variable did not refer specifically to eating with others but it aligns statistically with the other social integration items and including it in the index improves stratification of mortality [13]. The last item was whether or not participants were married (also counted in the network diversity score). Questions were scored as yes/no during that interval and yes responses were summed to create a social integration score. This score is strongly associated with all-cause mortality [13, 14] and with psychological well-being [31].

Loneliness was assessed by asking “In general, how often do you feel lonely? Always, usually, sometimes, never.” Similar items are used in public health surveys [32] and this single item assessment is strongly associated with depression and depressive symptoms even when statistically controlling for other social relationship variables [33, 34] and loneliness is linked to a weaker immune response to influenza vaccine [35].

Detection of S. aureus

Methods and results for S. aureus sampling are detailed in Russakoff et al. [6]. Briefly, two double tipped BBL CultureSwab™ swabs were used for sampling each of three different body sites (nares, throat, and hand). Swabbing was supervised by study staff (who worked in pairs) who also ensured that the self-swabbing was completed properly, i.e., swabbing each site for twenty seconds. Self-swabbing was performed because potential participants are more likely to enroll if they swab themselves and because participants are more likely to swab effectively relative to staff members who might attempt to avoid eliciting a sneeze or causing a gag reflex. Staff supervised swabbing, directing participants to rotate and move the swab around for the full 20 seconds at each site likely further improved sampling effectiveness. The high colonization prevalence is a testament to the success of this method and the quality control protocols. One double tipped swab was used for culturing while the other was used for DNA-based direct detection of S. aureus. While in the field, all swabs were stored on ice. In the laboratory, the double tipped swab destined for DNA-based detection was stored at -70°C before DNA extraction and detection. For direct detection of S. aureus, we used SaQuant, a quantitative real-time PCR assay with 95.6% sensitivity and 99.9% specificity [6, 36]. The other double tipped swab, destined for culturing, was stored at 4°C in the laboratory for no more than 48 hours before culturing to maximize the likelihood of cell survival [37]. For culturing, swabs were streaked onto CHROMagar S. aureus media and incubated for 24 hours at 37°C. CHROMagar Staph aureus chromogenic media allows for differentiation of S. aureus from other species as S. aureus colonies appear pink to mauve while other bacterial species are inhibited or will appear colorless or blue. Details on efforts to prevent false positive results are detailed in Russakoff et al. [6] and include whole genome sequencing and MLST v2.0 and SCCmecFinder v1.2 analyses (www.genomicepidemiology.org) of putative S. aureus colonies [38]. For samples that were culture negative but SaQuant positive, an amplicon sequencing approach was used to verify species designation [6] as well as extensive validation of the SaQuant assay to ensure accurate classification on samples with low S. aureus quantities [6, 36]. Individuals were recorded as being colonized by S. aureus if any of the swabs from any of the three body sites tested positive for S. aureus using the SaQuant assay or culture. Culture positive samples where the paired double tipped swab tested negative for SaQuant were counted as negative if the culture was confirmed as not S. aureus by whole genome sequencing.

Data reduction and analysis

To ensure reasonable numbers of positive S. aureus cases in social relationship strata, social relationship variables were collapsed into smaller categories. A 6 category social integration variable was created by combining the lowest 4 groups (i.e., 0–3, 4, 5, 6, 7 & 8), a 6 category network diversity score was created by collapsing the lowest and highest categories (0–4, 5, 6, 7, 8, 9–12) and the often and always lonely groups were also combined. Similarly, the network size variable was reduced to 5 categories with approximately equal numbers in each category (cutoffs of 0–15, 16–21, 22–25, 26–33, 34–65) (Table 1). All social relationship variables met an interval assumption (could be modeled as a single variable with multiple levels) [39] and were therefore entered as individual terms in all regression models.

Table 1. Sample sociodemographic characteristics.

Characteristic	Total	S. aureus negative	S. aureus positive
Participants, n	443	156	287
Age y, mean (SD)	36.4 (15.1)	38.7 (16.7)	35.2 (14.0)
Female sex, % (N)	52.6 (233)	66.0 (103)	45.3 (130)
Hispanic ethnicity, % (N)
No	29.8 (132)	20.5 (32)	34.8 (100)
Yes	68.4 (303)	75.6 (118)	64.5 (185)
Missing	1.8 (8)	3.8 (6)	0.7 (2)
Race, % (N)
White	66.8 (296)	62.8 (98)	69.0 (198)
Black	1.1 (5)	1.3 (2)	1.0 (3)
Native American	0.5 (2)	0.6 (1)	0.3 (1)
Asian	1.6 (7)	1.9 (3)	1.4 (4)
Pacific Islander	0.2 (1)	0.0 (0)	0.3 (1)
Other race	4.3 (19)	7.1 (11)	2.8 (8)
Multiple race	3.8 (17)	2.6 (4)	4.5 (13)
No preferred race	9.9 (44)	9.6 (15)	10.1 (29)
Missing	11.7 (52)	14.1 (22)	10.5 (30)
Education level, % (N)
< High school	12.0 (53)	17.9 (28)	8.7 (25)
High school diploma	14.0 (62)	16.0 (25)	12.9 (37)
Some college	50.8 (225)	40.4 (63)	56.4 (162)
College graduate or higher	23.0 (102)	25.0 (39)	22.0 (63)
Missing	0.2 (1)	0.6 (1)	0.0 (0)
Marital status, % (N)
Married/cohabiting	60.7 (269)	51.3 (80)	65.9 (189)
Divorced/separated	5.9 (26)	7.7 (12)	4.9 (14)
Widowed	1.4 (6)	3.2 (5)	0.3 (1)
Never married	25.3 (112)	26.3 (41)	24.7 (71)
Missing	0.9 (4)	1.3 (2)	0.7 (2)
Employed, % (N)	78.8 (349)	71.2 (111)	82.9 (238)
Language use at home, % (N)
Only Spanish	17.2 (76)	27.6 (43)	11.5 (33)
More Spanish than English	13.3 (59)	15.4 (24)	12.2 (35)
Equal Spanish and English	23.3 (103)	21.8 (34)	24.0 (69)
More English than Spanish	13.8 (61)	14.1 (22)	13.6 (39)
Only English	32.3 (143)	21.2 (33)	38.3 (110)
Other	0.2 (1)	0.0 (0)	0.3 (1)
Language of survey, % (N)
Spanish	30.0 (133)	44.2 (69)	22.3 (64)
English	70.0 (310)	55.8 (87)	77.7 (223)
Social integration score, % (N)
1–3	6.3 (28)	9.0 (14)	4.9 (14)
4	6.5 (29)	5.8 (9)	7.0 (20)
5	20.1 (89)	21.2 (33)	19.5 (56)
6	25.3 (112)	22.4 (35)	26.8 (77)
7	28.2 (125)	30.1 (47)	27.2 (78)
8	13.5 (60)	11.5 (18)	14.6 (42)
Social network diversity score, % (N)
0–4	18.3 (81)	19.9 (31)	17.4 (50)
5	17.8 (79)	17.3 (27)	18.1 (52)
6	16.9 (75)	18.6 (29)	16.0 (46)
7	17.4 (77)	19.9 (31)	16.0 (46)
8	14.0 (62)	12.2 (19)	15.0 (43)
9–12	15.6 (69)	12.2 (19)	17.4 (50)
Social network size, % (N)
0–15	15.1 (67)	17.9 (28)	13.6 (39)
16–21	20.1 (89)	21.8 (34)	19.2 (55)
22–25	16.9 (75)	12.8 (20)	19.2 (55)
26–33	24.6 (109)	27.6 (43)	23.0 (66)
34–65	23.3 (103)	19.9 (31)	25.1 (72)
Loneliness, % (N)
Never	57.1 (253)	60.3 (94)	55.4 (159)
Sometimes	36.3 (161)	31.4 (49)	39.0 (112)
Often/always	6.5 (29)	8.3 (13)	5.6 (16)
Self-rated health, % (N)
Poor/fair	11.1 (49)	16.0 (25)	8.4 (24)
Good	36.6 (162)	35.3 (55)	37.3 (107)
Very good	36.6 (162)	32.1 (50)	39.0 (112)
Excellent	15.6 (69)	16.0 (25)	15.3 (44)
Missing	0.2 (1)	0.6 (1)	0.0 (0)

Open in a new tab

Social integration score was derived from 8 items from the US National Health Interview Survey. Social network diversity and network size were measured using the Social Network Index [1].

Each social relationship variable was examined individually to predict binary S. aureus colonization, adjusting for age and sex. The fully adjusted models were of primary interest but unadjusted models are also reported. The main model was a generalized linear model using a Poisson family and a log link with robust clustered variance estimates. This model estimates prevalence ratios (labeled here incidence rate ratios) which are preferable to odds ratios derived from logistic regression [40], particularly when the outcome is common [41, 42]. Odds ratios also have the disadvantage of incorporating an arbitrary scaling factor that precludes odds ratio comparisons across models with different explanatory variables within a study, or comparing odds ratios across different studies [41, 43]. The clustered variance option adjusts the statistical tests to accommodate the group-level sampling. A two sided p-value of 0.05 was used to determine statistical significance. Stata 16.1 (Stata Corp) was used for all analyses. Post-hoc power analysis for 191 clusters (social groups) with a median cluster size of N = 3 and an intraclass correlation of S. aureus colonization of 0.14 has power > 0.89 to detect a 15% colonization difference.

Results

Sociodemographic characteristics of participants are in Table 1. Most participants (60.7%) were married, a slight majority (52.6%) were female, most (68.4%) reported Hispanic ethnicity and about a third (30%) chose to complete the Spanish version of the survey. Correlations among the social relationship indicators, self-rated health (SRH) and colonization with S. aureus are in Table 2.

Table 2. Correlations among social relationship variables, self-rated health and colonization with S. aureus.

	Network size	Social integration	Lonely	Self-rated health	S. aureus colonized
Social network diversity	0.69	0.53	-0.11	0.17	0.06
	(<0.001)	(<0.001)	(0.019)	(0.001)	(0.198)
Social network size		0.36	-0.11	0.19	0.06
		(<0.001)	(0.045)	(<0.001)	(0.226)
Social integration			-0.19	0.09	0.05
			(<0.001)	(0.073)	(0.254)
Lonely				-0.19	0.02
				(<0.001)	(0.730)
Self-rated health					0.07
					(0.159)

Open in a new tab

P-values in parentheses. Estimates adjusted for clustering. N’s = 442–443

Social relationships and self-rated health

Ordinary least squares regression models with clustered variance estimates were used to predict SRH with the 4 social relationship measures. Each of these was associated with SRH in adjusted models and all but social integration were associated in unadjusted models (Table 3). Overall, the social relationship resources were moderately correlated with one another, and as in other literature [23–25], were predictive of higher self-rated health. Similar findings were observed in sensitivity analyses using an ordinal logit model. Raw data are provided in S1 File.

Table 3. Coefficients regressing self-rated health on social relationship variables.

	Unadjusted			Adjusted for age and sex
	b	(95%CI)	p	b	(95%CI)	p
Social network diversity	0.09	(0.04–0.14)	0.001	0.08	(0.03–0.13)	0.001
Social network size	0.12	(0.06–0.19)	<0.001	0.10	(0.04–0.16)	0.001
Social integration	0.06	(-0.01–0.13)	0.073	0.07	(0.00–0.13)	0.044
Lonely	-0.28	(-0.41– -0.14)	<0.001	-0.32	(-0.45– -0.19)	<0.001

Open in a new tab

Ordinary least squares regression adjusted for clustering. N = 442

CI = confidence interval

Colonization with S. aureus

Overall 64.8% (n = 287) of the participants were colonized with S. aureus. Sample characteristics by S. aureus status are in Table 1. Raw data are provided in S1 File.

Social relationships and colonization with S. aureus

Neither social network diversity nor social network size were associated with S. aureus colonization (Table 4). The NHIS social integration variable and loneliness were also unrelated to S. aureus colonization. These patterns were consistent with and without adjustment for age and sex (Table 4). Log binomial models [44] predicting S. aureus colonization were almost identical to Poisson estimates and were also consistent when using indicator social relationship variables. Similar patterns were seen when using continuous social relationship variables (Table 4) and when covarying socioeconomic status markers (education and home ownership).

Table 4. Incidence rate ratios (IRR) regressing S. aureus colonization on individual social relationship variables.

				Adjusted for age and sex
	IRR	(95%CI)	p	IRR	(95%CI)	p
Categorical variables
Social network diversity	1.03	(0.99–1.07)	0.20	1.02	(0.98–1.06)	0.26
Social network size	1.03	(0.98–1.09)	0.23	1.02	(0.97–1.07)	0.56
Social integration	1.03	(0.98–1.08)	0.26	1.03	(0.98–1.08)	0.24
Lonely	1.02	(0.91–1.14)	0.73	1.02	(0.91–1.14)	0.74
Continuous variables
Social network diversity	1.03	(0.99–1.06)	0.12	1.02	(0.99–1.06)	0.15
Social network size	1.00	(1.00–1.01)	0.26	1.00	(1.00–1.01)	0.59
Social integration	1.03	(0.98–1.07)	0.29	1.03	(0.98–1.08)	0.26

Open in a new tab

All estimates are adjusted for clustering. N = 443

CI = confidence interval

Discussion

This study examined the association between S. aureus colonization and a number of social relationship resources that may denote exposure to infectious agents. There was no association of social network diversity with S. aureus colonization prevalence within naturally occurring social groups recruited from the community. S. aureus prevalence was also unrelated to loneliness, social network size, and social integration. These social relationship variables have previously been linked to a number of health outcomes including all-cause mortality [13, 23, 45]. In contrast, convergent validity was observed for all social relationship indicators via their positive associations with global SRH, the latter of which is both a clinical endpoint and robustly associated with mortality [20, 21, 46].

The hypothesis that more social interaction, and thus greater exposure, would be associated with higher S. aureus prevalence, was not supported. This was a strong test of the hypothesis given the sample reported a large average social network size and given that the association of network size and S. aureus colonization was nonsignificant and of very small magnitude. Household-level contacts are commonly linked to colonization and transmission of S. aureus [47–49], however little is known about the impact of social relationships outside the home or healthcare settings [50]. These results support the contention that social interactions outside the home (typical of social network assessments) are less important than those within the home for S. aureus colonization.

These data show that the salutary association observed between social network diversity and susceptibility to cold infection (found in only one study to date) does not extend to colonization with S. aureus. In prior work with colds, all participants were intentionally exposed to one of two cold viruses [1] whereas in the present study, exposure was naturally occurring. Thus, infectious challenge studies do not directly evaluate the link between social ties and a) the likelihood of coming in contact with an infected person or b) the chance of becoming infected given that contact [2, 51]. The present study did not examine clinical infection but preserved these two critical steps on the pathway, with step 2 being colonization rather than infection. Importantly, S. aureus colonization is outside the purview of immune system surveillance and thus is not informed by psychoneuroimmunology models.

This study is unique in that it examined the above mentioned social relationship resources in conjunction with S. aureus colonization in people living in a diverse border setting in southern Arizona. Potential participants were recruited from, and completed participation in, public and private spaces. Enrollees completed social relationship assessments and provided swabs from three body sites (hand, anterior nares, and throat) for S. aureus detection. No other health screening or eligibility restrictions were required. Thus, this data collection closely parallels the ecology from which S. aureus infection commonly arises and adds to our understanding of community transmission and prevalence by showing that social contacts as commonly assessed do not drive colonization. In a larger context, this work extends prior work on the link between social network resources and infection a) by examining a different infectious agent; b) by incorporating a broad assessment of social relationships; and c) by sampling within a multiethnic bilingual population.

This study has a number of strengths and limitations to consider. Colonization prevalence was substantially higher in this sample [6] relative to other estimates [5]. This is likely because of the greater sensitivity due to sampling from 3 different body sites and coupling molecular and culture-based detection methods, approaches that in combination are unique to this study [6, 52]. Greater colonization prevalence also indicates the effectiveness of self-swabbing quality controls. This study used the same measure of network diversity as in prior studies of infectious disease risk, and complemented that measure with additional social integration assessments and a subjective social relationship measure. As in other studies [53] correlations among these measures of quasi-objective and subjective social relationship resources were of small to medium magnitude (except for network size and diversity measures, which were strongly correlated with each other) and thus provide good coverage of different social relationship domains. The distribution of social integration in the present sample was similar to representative samples [14]. We had to collapse the lowest social integration categories but this was expected as very low social integration is rare, observed in less than 2% of the population [13].

This study was cross-sectional and did not include a clinical infectious outcome. It is therefore possible that clinical S. aureus infection, rather than colonization, is linked to social relationships. Recent work indicates that loneliness, but not social isolation, has a small but statistically significant association with a broad index of hospital-treated infections [54]. However, in that study loneliness was not associated with infections often caused by S. aureus, i.e., skin and soft tissue infections [55], thus providing convergent evidence that neither colonization nor putative S. aureus clinical infection are related to these social relationship resources. On a community level, this investigation of social relationship determinants of carriage in naturally occurring social groups, using a rigorous assessment of S. aureus colonization, illuminates the extent to which social relationships stratify community reservoirs of this important infectious agent.

Conclusions

In a sample of naturally occurring social groups within a community, this study did not find a statistically significant association between social network diversity and S. aureus colonization prevalence. The results also did not support the hypothesis that more social interaction would be associated with a higher S. aureus prevalence. Coupled, these findings suggest that, in this sample, structural social relationship characteristics and loneliness are not associated with colonization of S. aureus. Future research on S. aureus colonization should examine more intimate forms of social contact and longitudinal carriage to determine sources of transmission and ultimately, targeted mitigation strategies for persons at risk of infection.

Supporting information

S1 File. Raw data for the study.

(XLS)

Click here for additional data file.^{(351KB, xls)}

Acknowledgments

This work would not have been possible without the support from the Regional Center for Border Health in Somerton, AZ. The authors are grateful to the many field surveyors from NAU and the Regional Center for Border Health who recruited, sampled, and collected data from participants.

Abbreviations

MRSA: methicillin-resistant Staphylococcus aureus
MSSA: methicillin-susceptible Staphylococcus aureus
SNI: social network index
SRH: self-rated health
NHIS: National Health Interview Survey
PCR: polymerase chain reaction
DNA: deoxyribonucleic acid

Data Availability

All relevant data are within the paper and its Supporting Information files.

Funding Statement

This work was supported by the NAU Southwest Health Equity Research Collaborative, which is funded by the National Institute on Minority Health and Health Disparities at the National Institutes of Health (grant NIH U54MD012388). Funding was also received from the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (R15AI156771) The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

References

1.Cohen S, Doyle WJ, Skoner DP, Rabin BS, Gwaltney JM Jr., Social ties and susceptibility to the common cold. JAMA. 1997;277: 1940–4. [PubMed] [Google Scholar]
2.Edmunds WJ, Medley GF, O’Callaghan CJ. Social ties and susceptibility to the common cold. JAMA. 1997;278: 1231; author reply 2. doi: 10.1001/jama.278.15.1231b [DOI] [PubMed] [Google Scholar]
3.Tong SYC, Davis JS, Eichenberger E, Holland TL, Fowler VG. Staphylococcus aureus infections: epidemiology, pathophysiology, clinical manifestations, and management. Clin Microbiol Rev. 2015;28: 603–61. [DOI] [PMC free article] [PubMed] [Google Scholar]
4.Kourtis AP, Hatfield K, Baggs J, Mu Y, See I, Epson E, et al. Epidemiology and recent trends in methicillin-resistant and in methicillin-susceptible Staphylococcus aureus bloodstream infections—United States. MMWR. 2019;68: 214–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
5.Gorwitz RJ, Kruszon-Moran D, McAllister SK, McQuillan G, McDougal LK, Fosheim GE, et al. Changes in the prevalence of nasal colonization with Staphylococcus aureus in the United States, 2001–2004. J Infect Dis. 2008;197: 1226–34. [DOI] [PubMed] [Google Scholar]
6.Russakoff B, Wood C, Lininger MR, Barger SD, Trotter RT, Maltinsky S, et al. A quantitative assessment of Staphylococcus aureus community carriage in Yuma, Arizona. J Infect Dis. 2022. [DOI] [PMC free article] [PubMed] [Google Scholar]
7.Gualandi N, Mu Y, Bamberg WM, Dumyati G, Harrison LH, Lesher L, et al. Racial disparities in invasive methicillin-resistant Staphylococcus aureus infections, 2005–2014. Clin Infect Dis. 2018;67: 1175–81. [DOI] [PMC free article] [PubMed] [Google Scholar]
8.von Eiff C, Becker K, Machka K, Stammer H, Peters G. Nasal carriage as a source of Staphylococcus aureus bacteremia. N Engl J Med. 2001;344: 11–6. [DOI] [PubMed] [Google Scholar]
9.Perl TM, Cullen JJ, Wenzel RP, Zimmerman MB, Pfaller MA, Sheppard D, et al. Intranasal mupirocin to prevent postoperative Staphylococcus aureus infections. N Engl J Med. 2002;346: 1871–7. [DOI] [PubMed] [Google Scholar]
10.Wertheim HF, Melles DC, Vos MC, van Leeuwen W, van Belkum A, Verbrugh HA, et al. The role of nasal carriage in Staphylococcus aureus infections. Lancet Infect Dis. 2005;5: 751–62. [DOI] [PubMed] [Google Scholar]
11.Brissette I, Cohen S, Seeman TE. Measuring social integration and social networks. In: Cohen S, Underwood L, Gottlieb B, editors. Measuring and intervening in social support New York: Oxford University Press; 2000. p. 53–85. [Google Scholar]
12.Berkman LF, Glass T, Brissette I, Seeman TE. From social integration to health: Durkheim in the new millennium. Soc Sci Med. 2000;51: 843–57. doi: 10.1016/s0277-9536(00)00065-4 [DOI] [PubMed] [Google Scholar]
13.Barger SD. Social integration, social support and mortality in the US National Health Interview Survey. Psychosom Med. 2013;75: 510–7. doi: 10.1097/PSY.0b013e318292ad99 [DOI] [PubMed] [Google Scholar]
14.Barger SD, Uchino BN. Racial and ethnic variation in the association of social integration with mortality: ten-year prospective population-based US study. Sci Rep. 2017;7: 43874. doi: 10.1038/srep43874 [DOI] [PMC free article] [PubMed] [Google Scholar]
15.de Jong Gierveld J, Havens B. Cross-national comparisons of social isolation and loneliness: introduction and overview. Can J Aging. 2004;23: 109–13. doi: 10.1353/cja.2004.0021 [DOI] [PubMed] [Google Scholar]
16.de Jong-Gierveld J. Developing and testing a model of loneliness. J Pers Soc Psychol. 1987;53: 119–28. doi: 10.1037//0022-3514.53.1.119 [DOI] [PubMed] [Google Scholar]
17.Shankar A, McMunn A, Banks J, Steptoe A. Loneliness, social isolation, and behavioral and biological health indicators in older adults. Health Psychol. 2011;30: 377–85. doi: 10.1037/a0022826 [DOI] [PubMed] [Google Scholar]
18.DeSalvo KB, Bloser N, Reynolds K, He J, Muntner P. Mortality prediction with a single general self-rated health question. A meta-analysis. J Gen Intern Med. 2006;21: 267–75. doi: 10.1111/j.1525-1497.2005.00291.x [DOI] [PMC free article] [PubMed] [Google Scholar]
19.Goldberg P, Gueguen A, Schmaus A, Nakache JP, Goldberg M. Longitudinal study of associations between perceived health status and self reported diseases in the French Gazel cohort. J Epidemiol Community Health. 2001;55: 233–8. doi: 10.1136/jech.55.4.233 [DOI] [PMC free article] [PubMed] [Google Scholar]
20.Idler EL, Benyamini Y. Self-rated health and mortality: a review of twenty-seven community studies. J Health Soc Behav. 1997;38: 21–37. [PubMed] [Google Scholar]
21.Barger SD, Cribbet MR, Muldoon MF. Participant-reported health status predicts cardiovascular and all-cause mortality independent of established and nontraditional biomarkers: evidence from a representative US sample. J Am Heart Assoc. 2016;5: e003741. doi: 10.1161/JAHA.116.003741 [DOI] [PMC free article] [PubMed] [Google Scholar]
22.Haring R, Feng YS, Moock J, Volzke H, Dorr M, Nauck M, et al. Self-perceived quality of life predicts mortality risk better than a multi-biomarker panel, but the combination of both does best. BMC Med Res Methodol. 2011;11: 103. doi: 10.1186/1471-2288-11-103 [DOI] [PMC free article] [PubMed] [Google Scholar]
23.Laugesen K, Baggesen LM, Schmidt SAJ, Glymour MM, Lasgaard M, Milstein A, et al. Social isolation and all-cause mortality: a population-based cohort study in Denmark. Sci Rep. 2018;8: 4731. doi: 10.1038/s41598-018-22963-w [DOI] [PMC free article] [PubMed] [Google Scholar]
24.Sirven N, Debrand T. Social participation and healthy ageing: An international comparison using SHARE data. Soc Sci Med. 2008;67: 2017–26. doi: 10.1016/j.socscimed.2008.09.056 [DOI] [PubMed] [Google Scholar]
25.Gorman BK, Sivaganesan A. The role of social support and integration for understanding socioeconomic disparities in self-rated health and hypertension. Soc Sci Med. 2007;65: 958–75. doi: 10.1016/j.socscimed.2007.04.017 [DOI] [PubMed] [Google Scholar]
26.Platt JR. Strong inference: certain systematic methods of scientific thinking may produce much more rapid progress than others. Science. 1964;146: 347–53. doi: 10.1126/science.146.3642.347 [DOI] [PubMed] [Google Scholar]
27.Barger SD, Lininger MR, Trotter RT 2nd, Wayment HA, Mbegbu M, Kyman S, et al. Educational attainment and Staphylococcus aureus colonization in a Hispanic border community: testing fundamental cause theory. mSphere. 2020;5. [DOI] [PMC free article] [PubMed] [Google Scholar]
28.Pearson T, Barger SD, Lininger M, Wayment H, Hepp C, Villa F, et al. Health disparities in Staphylococcus aureus transmission and carriage in a border region of the United States based on cultural differences in social relationships: protocol for a survey study. JMIR Res Protoc. 2019;8: e14853. [DOI] [PMC free article] [PubMed] [Google Scholar]
29.Centers for Disease Control and Prevention. Behavioral Risk Factor Surveillance System, LLCP 2019 Codebook Report. 2020. Available from: https://www.cdc.gov/brfss/annual_data/2019/pdf/codebook19_llcp-v2-508.HTML.
30.National Center for Health Statistics, Division of Health Interview Statistics. 2001 National Health Interview Survey (NHIS) public use data release: Sample adult file. Hyattsville, Maryland 2003. Available from: https://ftp.cdc.gov/pub/Health_Statistics/NCHS/Survey_Questionnaires/NHIS/2001/qsamadlt.pdf.
31.Barger SD, Donoho CJ, Wayment HA. The relative contributions of race/ethnicity, socioeconomic status, health, and social relationships to life satisfaction in the United States. Qual Life Res. 2009;18: 179–89. doi: 10.1007/s11136-008-9426-2 [DOI] [PMC free article] [PubMed] [Google Scholar]
32.McGinty EE, Presskreischer R, Han H, Barry CL. Psychological distress and loneliness reported by US adults in 2018 and April 2020. JAMA. 2020;324: 93–4. doi: 10.1001/jama.2020.9740 [DOI] [PMC free article] [PubMed] [Google Scholar]
33.Barger SD, Messerli-Bürgy N, Barth J. Social relationship correlates of major depressive disorder and depressive symptoms in Switzerland: nationally representative cross sectional study. BMC Public Health. 2014;14: 273. doi: 10.1186/1471-2458-14-273 [DOI] [PMC free article] [PubMed] [Google Scholar]
34.Sjoberg L, Ostling S, Falk H, Sundh V, Waern M, Skoog I. Secular changes in the relation between social factors and depression: a study of two birth cohorts of Swedish septuagenarians followed for 5 years. J Affect Disord. 2013;150: 245–52. doi: 10.1016/j.jad.2013.04.002 [DOI] [PubMed] [Google Scholar]
35.Pressman SD, Cohen S, Miller GE, Barkin A, Rabin BS, Treanor JJ. Loneliness, social network size, and immune response to influenza vaccination in college freshmen. Health Psychol. 2005;24: 297–306. doi: 10.1037/0278-6133.24.3.297 [DOI] [PubMed] [Google Scholar]
36.Wood C, Sahl J, Maltinsky S, Coyne B, Russakoff B, Yague DP, et al. SaQuant: a real-time PCR assay for quantitative assessment of Staphylococcus aureus. BMC Microbiol. 2021;21: 174. doi: 10.1186/s12866-021-02247-6 [DOI] [PMC free article] [PubMed] [Google Scholar]
37.Panisello Yague D, Mihaljevic J, Mbegbu M, Wood CV, Hepp C, Kyman S, et al. Survival of Staphylococcus aureus on sampling swabs stored at different temperatures. J Appl Microbiol. 2021. [DOI] [PMC free article] [PubMed] [Google Scholar]
38.Pearson T, Hepp C, Trotter RT 2nd, Mbegbu M, Russakoff B, Panisello Yague D, et al. Genome sequences of community carriage strains of Staphylococcus aureus from Yuma, Arizona. Microbiol Resour Announc. 2021;10: e0044921. [DOI] [PMC free article] [PubMed] [Google Scholar]
39.Long JS, Freese J. Regression models for categorical outcomes using Stata. 2nd ed. College Station, TX: Stata Press; 2003. [Google Scholar]
40.Zou G. A modified poisson regression approach to prospective studies with binary data. Am J Epidemiol. 2004;159: 702–6. doi: 10.1093/aje/kwh090 [DOI] [PubMed] [Google Scholar]
41.Norton EC, Dowd BE, Maciejewski ML. Odds ratios-current best practice and use. JAMA. 2018;320: 84–5. doi: 10.1001/jama.2018.6971 [DOI] [PubMed] [Google Scholar]
42.Lininger MR, Root HJ, Camplain R, Barger SD. Describing the appropriate use and interpretation of odds and risk ratios. Res Sports Med. 2022: forthcoming. doi: 10.1080/15438627.2022.2132861 [DOI] [PubMed] [Google Scholar]
43.Norton EC, Dowd BE. Log odds and the Interpretation of logit models. Health Serv Res. 2018;53: 859–78. doi: 10.1111/1475-6773.12712 [DOI] [PMC free article] [PubMed] [Google Scholar]
44.Petersen MR, Deddens JA. A comparison of two methods for estimating prevalence ratios. BMC Med Res Methodol. 2008;8: 9. doi: 10.1186/1471-2288-8-9 [DOI] [PMC free article] [PubMed] [Google Scholar]
45.Holt-Lunstad J, Smith TB, Baker M, Harris T, Stephenson D. Loneliness and social isolation as risk factors for mortality: a meta-analytic review. Perspect Psychol Sci. 2015;10: 227–37. doi: 10.1177/1745691614568352 [DOI] [PubMed] [Google Scholar]
46.Benyamini Y, Idler EL. Community studies reporting association between self-rated health and mortality: additional studies, 1995 to 1998. Res Aging. 1999;21: 392–401. [Google Scholar]
47.Knox J, Uhlemann AC, Lowy FD. Stopping household methicillin-resistant Staphylococcus aureus transmission and recurrent infections: an unmet challenge. Clin Infect Dis. 2021;73: e4578–e80. [DOI] [PMC free article] [PubMed] [Google Scholar]
48.Ng W, Faheem A, McGeer A, Simor AE, Gelosia A, Willey BM, et al. Community- and healthcare-associated methicillin-resistant Staphylococcus aureus strains: An investigation into household transmission, risk factors, and environmental contamination. Infect Control Hosp Epidemiol. 2017;38: 61–7. [DOI] [PubMed] [Google Scholar]
49.Shankar N, Chow ALP, Oon J, Hsu LY, Ang B, Pang J, et al. The epidemiology and transmission of methicillin-resistant Staphylococcus aureus in the community in Singapore: study protocol for a longitudinal household study. BMC Infect Dis. 2017;17: 678. [DOI] [PMC free article] [PubMed] [Google Scholar]
50.Knox J, Uhlemann AC, Lowy FD. Staphylococcus aureus infections: transmission within households and the community. Trends Microbiol. 2015;23: 437–44. [DOI] [PMC free article] [PubMed] [Google Scholar]
51.Noppert GA, Kubale JT. Incorporating social environment data in infectious disease research. Lancet Public Health. 2023;8: e88–e9. doi: 10.1016/S2468-2667(23)00005-1 [DOI] [PMC free article] [PubMed] [Google Scholar]
52.Popovich KJ, Aroutcheva A, Hota B, Beavis KG, Hayden MK, Weinstein RA. Anatomic sites of colonization with community-associated methicillin-resistant Staphylococcus aureus. Infect Control Hosp Epidemiol. 2014;35: 1192–4. [DOI] [PMC free article] [PubMed] [Google Scholar]
53.Coyle CE, Dugan E. Social isolation, loneliness and health among older adults. J Aging Health. 2012;24: 1346–63. [DOI] [PubMed] [Google Scholar]
54.Elovainio M, Komulainen K, Sipila PN, Pulkki-Raback L, Cachon Alonso L, Pentti J, et al. Association of social isolation and loneliness with risk of incident hospital-treated infections: an analysis of data from the UK Biobank and Finnish Health and Social Support studies. Lancet Public Health. 2023;8: e109–e18. doi: 10.1016/S2468-2667(22)00253-5 [DOI] [PMC free article] [PubMed] [Google Scholar]
55.Ki V, Rotstein C. Bacterial skin and soft tissue infections in adults: A review of their epidemiology, pathogenesis, diagnosis, treatment and site of care. Can J Infect Dis Med Microbiol. 2008;19: 173–84. doi: 10.1155/2008/846453 [DOI] [PMC free article] [PubMed] [Google Scholar]

PLoS One. doi: 10.1371/journal.pone.0284400.r001

Decision Letter 0

Samiullah Khan

31 Jan 2023

PONE-D-23-00421Cross-sectional study of the association of social relationship resources with Staphylococcus aureus colonization in naturally occurring social groupsPLOS ONE

Dear Dr. Steven D Barger,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

==============================

ACADEMIC EDITOR:

Dear author,

Please read the comments of both reviewers carefully, revise the manuscript in light of reviewer's comments. Submit the revised manuscript and rebuttal letter. The submitted revised manuscript will be re-reviewed before acceptance.

==============================

Please submit your revised manuscript by Mar 17 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Samiullah Khan, Ph. D

Academic Editor

PLOS ONE

Journal requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. Please provide additional details regarding participant consent. In the ethics statement in the Methods and online submission information, please ensure that you have specified what type you obtained (for instance, written or verbal, and if verbal, how it was documented and witnessed). If your study included minors, state whether you obtained consent from parents or guardians. If the need for consent was waived by the ethics committee, please include this information.

Once you have amended this/these statement(s) in the Methods section of the manuscript, please add the same text to the “Ethics Statement” field of the submission form (via “Edit Submission”).

For additional information about PLOS ONE ethical requirements for human subjects research, please refer to http://journals.plos.org/plosone/s/submission-guidelines#loc-human-subjects-research.

3. We note that you have stated that you will provide repository information for your data at acceptance. Should your manuscript be accepted for publication, we will hold it until you provide the relevant accession numbers or DOIs necessary to access your data. If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide.

4. We note that you have included the phrase “data not shown” in your manuscript. Unfortunately, this does not meet our data sharing requirements. PLOS does not permit references to inaccessible data. We require that authors provide all relevant data within the paper, Supporting Information files, or in an acceptable, public repository. Please add a citation to support this phrase or upload the data that corresponds with these findings to a stable repository (such as Figshare or Dryad) and provide and URLs, DOIs, or accession numbers that may be used to access these data. Or, if the data are not a core part of the research being presented in your study, we ask that you remove the phrase that refers to these data.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Partly

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: No

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: No

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This relates to a manuscript entitled Cross-sectional study of the association of social relationship resources with Staphylococcus aureus colonization in naturally occurring social groups.

General comment

Topic of the manuscript is attractive to certain extent. But has some grey areas that need improvisation.

It is well known that mere colonization of S. aureus will not lead to any kind of infections in a health population. It is mainly associated with patient and microbial related factors. eg. Hospitalization/Immunodeficiency/metabolic disorders/ drug resistance- MRSA/VRSA

Since the study population is healthy, what is the rationale of this research

Moreover, in the introduction the authors have mentioned that i/3rd of the US population is colonized with S. aureus.

Mode of transmission and factors that trigger the transmission rate associated with S. aureus is already know. And S. aureus infection is not a contagious disease too. By maintaining proper hand hygiene or by decolonization this can be managed to a greater extent.

Above all, the results of the research are inconclusive and shallow.

In this context, what is the relevance of this research?

Specific comment

� Strictly follow the journal’s instructions for formatting the abstract and other parts

� The English portion of the article need to be improved

Title

Modify the title by precisely showing the study settings and study population

Abstract

Has to be narrate properly. Methodology and conclusion part needs to be re-written

Introduction

Introduction: It needs to be more informative

It is too general, broad and shallow.

Organize according to the objectives of the study.

Update the reference

Rationale has to be more emphasized.

State the precise problems existing in the study population or area

Research gap existing in the study area.

Materials and methods

1. It is mandatory to include the details sample size calculation

2. Inclusion and exclusion criteria has to be precisely mentioned.. Why authors excluded children

3. Have you included any participants under decolonization procedure

4. Study was conducted during the wake of covid outbreaks… Have you taken any precautionary measures for collecting nare samples Ɂ

5. Why you prefer self-sampling

6. How you maintain the quality of sample

7. Statistical analysis is unclear

8. Cite the Tables properly

9. Have you checked antimicrobial susceptibility profile of positives cases with regard to MRSA/VRSA

10. Have authors recommended decolonization of positive cases

11. Status of MRSA and VRSA and co-resistance profiles have to be included

Results

Please pinpoint the most relevant results rather than incurious findings

Discussion

Need substantial improvement.

Please improve the main conclusion of the manuscript.

Reviewer #2: 1. The study appears to be well-conducted, but I recommend updating the references section to include more recent research on the topic. This will provide a more complete and current understanding of the subject and will also help to strengthen the overall credibility of the study.

2. The results of the manuscript appear to be weak and it would be beneficial to update the study with more recent findings. It is also important to highlight the use of whole genome sequencing in the results section, as it is a significant aspect of the study that should be emphasized and discussed in relation to the findings. This will help to strengthen the overall validity and impact of the study.

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Attachment

Submitted filename: PONE-D-23-00421.docx

Click here for additional data file.^{(140.1KB, docx)}

PLoS One. 2023 Apr 13;18(4):e0284400. doi: 10.1371/journal.pone.0284400.r002

Author response to Decision Letter 0

4 Mar 2023

March 4, 2023

Samiullah Khan, Ph.D

Academic Editor

PLOS ONE

Dear Dr. Khan:

We are grateful to have the opportunity to revise our PLOS ONE submission titled “Cross-sectional study of the association of social relationship resources with Staphylococcus aureus colonization in naturally occurring social groups” and we are thankful to the Editor and Reviewers for their feedback. Our responses to Editor requests and reviewers’ comments are below. As instructed, we uploaded three files comprising the rebuttal letter, the revised document with tracked changes, and the revised document without tracked changes. We also included a supplemental file containing the raw data used for our study.

Editor comments:

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming.

We reviewed the PLOS ONE style requirements and believe we have complied with those guidelines.

We note that participants provided verbal informed consent that was documented by two staff members. We now include the IRB project number in the Study Overview section. This manuscript was restricted to persons 18 years of age or older.

We included the raw data as a supplementary file with the resubmission. It is titled S1 Dataset.

4. We note that you have included the phrase “data not shown” in your manuscript. Unfortunately, this does not meet our data sharing requirements. PLOS does not permit references to inaccessible data. … Or, if the data are not a core part of the research being presented in your study, we ask that you remove the phrase that refers to these data.

We did not intend to refer to inaccessible data, but rather to sensitivity analyses of the main data using different statistical models. We apologize that this was unclear. Those analyses confirmed the findings from the main statistical models, but were not included in the manuscript. We report these sensitivity analyses to increase the rigor of our study, i.e., to demonstrate our findings were not driven by the analytic approach. We removed the phrasing about not showing the data and also include the raw data in the resubmission.

In the brief checklist the reviewers disagreed with the statement that the statistical analysis was “performed appropriately and rigorously.” Although no specific examples were provided, we highlight our optimal statistical practices here. First, for the binary colonization outcome variable we used a generalized linear model to generate rate ratios. This is preferable to a logistic regression model producing odds ratios, as odds ratios are biased when the base rate of the binary outcome is > 10% (JAMA, 2018. 320(1): p. 84-8; Am J Epidemiol, 2004. 159(7): p. 702-6) and do not produce coefficients that are comparable across statistical models, either within or across studies. As shown in the Zou (2004) reference, our GLM approach is unbiased and has good coverage of the nominal 95% confidence intervals. We elaborated on the disadvantages of odds ratios in the revised manuscript, adding additional references to support this approach. In fact, two members of our team (SDB and MRL) recently published a primer describing optimal analytic practices for binary outcomes-that reference is included in the revision.

There are additional analytic features that indicate rigor. We incorporated clustering in our analyses because the potential lack of independence of our participants, who were recruited in small groups. We evaluated the functional form of the explanatory variables in the models, confirming appropriate model specification. We also tested alternative but related statistical models for both colonization and self-rated health (log binomial and cumulative logit models, respectively) which confirmed the main analyses. We are confident these data are analyzed transparently, optimally, and that our findings are not driven by arbitrary analytic or data reduction choices.

Reviewer comments

General comment

Topic of the manuscript is attractive to certain extent. But has some grey areas that need improvisation.

It is well known that mere colonization of S. aureus will not lead to any kind of infections in a health [sic] population. It is mainly associated with patient and microbial related factors. eg. Hospitalization/Immunodeficiency/metabolic disorders/ drug resistance- MRSA/VRSA

Since the study population is healthy, what is the rationale of this research

Moreover, in the introduction the authors have mentioned that i/3rd of the US population is colonized with S. aureus.

1. Unfortunately, this reviewer’s understanding of the problems, challenges, and knowledge gaps is not aligned with the consensus opinions of public health agencies and researchers. While colonization of S. aureus does not necessarily lead to infection, it is a major risk factor. This principal has guided mitigation practices that have reduced infections in health care populations over the last 15 years. Unfortunately, progress in healthcare settings has slowed, and an increase in community acquired cases is cause for alarm and suggestive of an important reservoir outside of the healthcare setting and into the community (Kourtis et al. MMWR. 2019;68:214-9.). For this reason, research is now increasingly being focused on understanding infections and the spread of S. aureus in the community. Our previous work has established that ~65% of community members in southern Arizona may be colonized, with significant ethnic and sex-based disparities. This prevalence is much higher than previously reported, and likely reflects a combination of singleton site sampling and the inadequacy of culture-based colonization ascertainment in prior studies. In fact, our earlier work shows that almost half of culture-negative assays were positive for S. aureus when evaluated with qPCR (Russakoff et al. J Infect Dis 2022).

We have a very poor understanding about who is colonized, why they may be colonized, and whether the pathogen is likely to spread to other body sites, be transmitted to other people, or cause infections. Our work here is to address perhaps the most important hypothesis about the spread of an infectious disease – whether social interactions are likely to result in spread and higher rates of colonization. Our results are definitive in that the types of social interactions studied here do not impact the likelihood of carriage. This has an important bearing on design of future studies and mitigation efforts. These points are all made in the introduction and in the abstract.

Mode of transmission and factors that trigger the transmission rate associated with S. aureus is already know [sic].

2. This is definitely not true. We have very little understanding of mechanisms and precise sources of transmission and even transmission rates. Our qPCR validation assays show that we do not accurately understand even carriage in the population, let alone transmission modes (see above). This is why community-acquired infections are on the rise and likely why even the effectiveness of healthcare-associated infection control efforts have plateaued. Even sampled body sites are inconsistent from study to study, thus obscuring the true prevalence in the community. We have two funded NIH grants (see Funding section) to address these significant needs and other funding agencies are pouring significant amounts of money into research to address these very questions which are foundational to efforts that explore decolonization and pathogen reduction as a strategy to prevent infection (see Topics 22.4 and 22.5 in the latest CDC BAA which can be downloaded at this site https://sam.gov/opp/15229982f7c348f69fd35e9a0add8aba/view). (Also see the FDA and CDC sponsored workshop: https://info.rescueagency.com/en-us/drug-development-consideration-virtual-public-workshop-cdc-fda#description).

And S. aureus infection is not a contagious disease too.

3. This is not true, although we are a little confused by this statement as it is the bacteria that are contagious and not the disease. While we know that S. aureus can be transmitted, we have only a very rudimentary understanding of the mechanisms. Importantly, this work is about carriage and not infection. We make this distinction throughout the paper (including in the very first sentence of the abstract) and discuss why understanding carriage has important implications on infections.

By maintaining proper hand hygiene or by decolonization this can be managed to a greater extent.

4. We are surprised that the reviewer makes this point about controlling contagious diseases after incorrectly stating in his/her previous point that S. aureus is not contagious. Unfortunately, the infection rate data (Kourtis et al. 2019) and the request by funding agencies for research to better understand and mitigate the spread of S. aureus demonstrate that this statement is inaccurate. There is very little evidence on what body sites act as sources, but current understanding indicates the hands are probably not a significant source. Decolonization has a lot of potential, but has thus far fallen short of expectations because we need to better understand community carriage. The necessity of this point is evidenced by the latest call for proposals by the CDC soliciting work to better characterize carriage so that decolonization can be more efficient. Please see Topic 22.5 in the CDC BAA which can be downloaded at this site (https://sam.gov/opp/15229982f7c348f69fd35e9a0add8aba/view). More broadly, community onset infection is an important element of ongoing S. aureus surveillance efforts in the U.S., which encompasses 16 million persons (https://www.cdc.gov/hai/eip/saureus.html).

Above all, the results of the research are inconclusive and shallow.

5. We respectfully disagree. Our research is conclusive that the types of social interactions that we consider are not correlated with the likelihood of being colonized. We’re not sure what the reviewer means by “shallow”. As shown in other studies, our social relationship assessments have substantial prognostic value for clinical health endpoints including depression, infectious disease susceptibility, and mortality. Thus, our battery of social relationship assessments is optimal, and provides a strong test of whether these are associated with S. aureus colonization. As noted below, any association of e.g., loneliness with clinical infection is probably quite small.

In this context, what is the relevance of this research?

5. Please refer to our point #1 above.

Specific comment

� Strictly follow the journal’s instructions for formatting the abstract and other parts

6. As noted above we reviewed the manuscript and it should conform to formatting guidelines.

� The English portion of the article need [sic] to be improved

7. All co-authors reviewed the document and provided editorial input. We feel that the article is written clearly and succinctly. Given that this reviewer did not provide specific examples we did not undertake any English-language revision.

Title

Modify the title by precisely showing the study settings and study population

8. The title describes the study design, the research question and the small group sampling approach. We added “along the US/Mexico border” to the title to further identify the setting.

Abstract

Has to be narrate [sic] properly. Methodology and conclusion part needs to be re-written

9. Without specific examples, this comment is not actionable. We have clearly defined subsections of the methodology to organize the manuscript in a reader-friendly manner.

Introduction

Introduction: It needs to be more informative

It is too general, broad and shallow.

10. These are sweeping statements that are not actionable without specifying what elements the reviewer feels need more coverage. We believe that we have provided sufficient background to: a) understand the competing ways in which social network resources can impact health, b) understand the relative aspects of S. aureus biology and epidemiology, c) describe and justify the social network assessments that we used, and d), describe the potential implications of the work depending on different possible outcomes. We clearly delineate multiple competing hypotheses in the introduction, which aligns with the approach found in other studies of social relationships and infectious pathogens (Lancet Public Health. 2023;8: e109-e18).

Organize according to the objectives of the study.

11. There is only one objective to this study which is laid out clearly in the title and abstract. We use the introduction to provide background for this objective.

Update the reference

12. Our reference #35 referred to a submitted manuscript. This was an error as it was published in 2021. We corrected this. More broadly, our current understanding of S. aureus carriage in the US population is largely based on the 2001–2002 National Health and Nutrition Examination Survey (NHANES), hence that reference is from 2008. Unfortunately, there aren’t more recent population-based estimates. We do however contrast those findings with our own recent work that we discuss and cite. Our revised manuscript also incorporates a paper published after we submitted our manuscript. That paper evaluates the association of social isolation and loneliness with infectious disease related hospitalization (see last paragraph of Discussion section). Requests to “update” other references are not applicable as these citations are for established theoretical models of social relationships (Brissette; Berkman).

Rationale has to be more emphasized.

13. We believe that the rationale is clearly laid out in the abstract and introduction. Furthermore, at the end of the introduction, we discuss how different outcomes will have different implications on our understanding of S. aureus transmission and will translate into more efficient and targeted mitigation practices (see also point 1 above). By describing and testing several working hypotheses (last paragraph of Introduction), we model optimal scientific practices (Science 1964;146(3642):347-53), avoiding the confirmatory biases that underlie most scientific literature (Scientometrics (2012) 90:891–904; Nat Hum Behav (2019) 3:197). In fact, we chose PLOS ONE as a publication outlet because its policies are specifically designed to remedy systemic biases in scientific publication.

State the precise problems existing in the study population or area

14. We are confused by this comment as this work is not about identifying problems in a specific study population, but rather, using a population to test a specific hypothesis that is well laid out in the introduction and abstract.

Research gap existing in the study area.

15. The knowledge gaps that this work addresses are well described in the introduction and abstract. For example, in the 2nd paragraph of the introduction we note “…we address gaps in our understanding of the links between social resources and infectious diseases by examining the association of social network diversity with colonization by Staphylococcus aureus in naturally occurring groups of community residents.” It is unknown the extent to which social connections are linked to infectious pathogens in naturally occurring social groups.

Materials and methods

It is mandatory to include the details sample size calculation

16. We did not conduct a priori power calculations as we had no prior estimate of the group-level intraclass correlation for staph colonization. Our data collection was also prematurely terminated due to the COVID lockdown. However, in the revised manuscript we now include post hoc power calculations, showing substantial power to detect colonization differences on par with the ethnic disparity seen in our data.

Inclusion and exclusion criteria has to be precisely mentioned.. Why authors excluded children

17. In the participant section, we state that “groups of two or more people who appeared to be together were invited by study staff to participate in the study”. We also state the reason why children were excluded (“Children were eligible to participate but because their survey responses were often completed by adult proxy respondents we restrict our analysis to adults 18 years and over”). These were the only inclusion/exclusion criteria. We also provide a citation to another report in case a reader would like details that may not be pertinent here.

Have you included any participants under decolonization procedure

18. None of the participants told us that they were undergoing decolonization for S. aureus.

Study was conducted during the wake of covid outbreaks… Have you taken any precautionary measures for collecting nare samples Ɂ

19. We did not as all samples were collected before March, 2020 (pre-COVID). Study dates have been added to the Study Overview section.

Why you prefer self-sampling

20. We have added a statement about this in the text. In short, participants are more likely to participate if they can control sampling. Most importantly, self-sampling was clearly successful as prevalence rates in these data are much higher than in previous studies. Ineffective sampling would have the opposite effect.

How you maintain the quality of sample

21. We do this by a) having 2 staff members supervise sample collection, b) ensuring that swabbing is done for 20 seconds, and c) placing the sample on ice for immediate transfer to the laboratory. The high S. aureus prevalence in our data clearly show the success of our sampling. We added these points to the methods section and the discussion section.

Statistical analysis is unclear

22. Details on where the reviewer struggled to understand would help us address this concern. As noted above, we elaborated on the rigor of our statistical approach in the revised manuscript. We also added language describing the statistical limitations of using odds ratios to quantify the association between social relationships and colonization.

Cite the Tables properly

23. All Tables are now cited as per the PLOS ONE style guidelines. There were two instances where we wrote “see Table” – we deleted “see”.

Have you checked antimicrobial susceptibility profile of positives cases with regard to MRSA/VRSA

24. We have not. There are many additional ways that we could characterize recovered strains, but this is beyond the scope of this work. See also our response below.

Have authors recommended decolonization of positive cases

25. We did not, because a) this isn’t a clinical trial, b) these are otherwise healthy community members, and c) the assays are for research only and not approved for diagnostic testing. Decolonization (of MRSA) is for high risk patient populations not otherwise healthy community members and our ethical approval and funding did not encompass active surveillance testing for decolonization purposes. Decolonization is well outside the ethical and legal authority of our study.

Status of MRSA and VRSA and co-resistance profiles have to be included

26. We disagree for a number of reasons. First, while drug resistant strains will influence treatment of infections, there is no reason to believe that they impact carriage differently from drug sensitive strains. Second, the prevalence of drug resistant strains is very low and parsing out the data in this way would not be diagnostic (given at most a handful of MRSA isolates). Third, drug resistant strains have evolved independently multiple times from drug sensitive strains. Therefore, two MRSA strains may be more epidemiologically different from each other than a drug resistant and drug sensitive strain.

Results

Please pinpoint the most relevant results rather than incurious findings

27. Each of social relationship assessments has strong prognostic value for clinical endpoints, with the possible exception of social network size. Thus, our study includes the most potent social relationship resources and they are described in turn without emphasizing one over the other. We are not sure what an “incurious finding” is, unless this alludes to the null findings we report, which are encouraged by PLOS ONE policy.

Discussion

Need [sic] substantial improvement.

Please improve the main conclusion of the manuscript.

28. We clearly state in the last paragraph that “structural social relationships and loneliness are not associated with colonization of S. aureus.” Because no specifics were provided for these comments, we did not further edit the discussion except for the addition of a new study (published after our initial submission) that also looks at the association of structural social relationships and loneliness with hospital-treated infection. This very large study found a small association of loneliness, but not social isolation, with hospital-treated infection. Looking more closely, the loneliness association was not observed when considering skin and soft tissue infections, which are mostly likely driven by S. aureus. Our data align with this new study, and provide a bridge between clinical infection and colonization.

29. We are grateful to Reviewer 2 for the compliment. We assume that the reviewer is referring to our citations of estimates of prevalence in the US. Unfortunately there have not been more recent estimates, and the work that we cite is the most comprehensive estimate to date. We do however cite our previous work based in Arizona. No studies have addressed the connection between social network resources and carriage of S. aureus – our work is completely novel. As noted above, after we submitted our study, a study was published examining social relationships and infectious disease. That paper also notes the paucity of research in the area, and the only recent work on infection and social ties is related to COVID. We are aware of no other studies looking at colonization and social relationships, and if you search PubMed for these terms the only paper identified is an earlier paper from our group.

30. We are not sure what the reviewer means by a “weak” result. We assume that he/she is referring to our inability to reject our null hypothesis? PLOS One clearly has an inclusive scope where “negative and null results are all in scope.“ Despite this, the implications of our work for mitigation practices are profound as we can conclude that casual social relationships are not likely to result in transmission. This work is very recent and represents our most recent findings. As noted above there is a paucity of published work on social relationships and infectious diseases, specifically pathogen carriage. We would be grateful for specific related references that are more recent but our literature search efforts do not uncover any.

Our whole genome sequencing results are only peripherally relevant to this work. The sequencing was done to validate our detection assay and is detailed elsewhere. What is relevant to this work is the sensitivity and specificity of our detection assay, and that has been detailed in 2 other publications that are cited. The excellent classification accuracy of our laboratory procedures indeed strengthens the validity of our work. Conversely, since this work is about carriage and social relationship resources, genome sequencing per se does not play a role and its inclusion would be a distraction.

There were other miscellaneous comments in a MS Word copy of the manuscript returned to the authors in the editorial decision email. These comments have been addressed above and in the manuscript (e.g., the Figure caption, which is now called a STROBE flow diagram as per the STROBE guidelines (cf. PLOS ONE 14(10): e0222359); elaborating on the self-swabbing p.10 ).

Thank you for your consideration.

Sincerely,

Steven D. Barger PhD

Professor of Psychology

Steven.Barger@nau.edu

Department of Psychology

Northern Arizona University

(928) 523-9619 tel

(928) 523-6777 fax

Attachment

Submitted filename: Response to Reviewers.docx

Click here for additional data file.^{(244.7KB, docx)}

PLoS One. doi: 10.1371/journal.pone.0284400.r003

Decision Letter 1

Samiullah Khan

21 Mar 2023

PONE-D-23-00421R1Cross-sectional study of the association of social relationship resources with Staphylococcus aureus colonization in naturally occurring social groupsPLOS ONE

Dear Dr. Barger,

Please incorporate the following minor corrections so that the manuscript would be acceptable for publication.

1. First person pronouns have been used frequently, the manuscript should be written anonymously and use of first person must be very limited.

2. Inclusion and exclusion criteria has to be precisely mentioned. Please submit your revised manuscript by May 05 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

We look forward to receiving your revised manuscript.

Kind regards,

Dario Ummarino, PhD

Senior Editor

PLOS ONE

On behalf of,

Dr. Samiullah Khan

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments:

Dear Author,

Incorporate the following minor corrections so that the manuscript would be acceptable for publication.

1. First person pronouns have been used frequently, the manuscript should be written anonymously and use of first person must be very limited.

2. Inclusion and exclusion criteria has to be precisely mentioned.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: (No Response)

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

Reviewer #1: Partly

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

Reviewer #1: No

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Reviewer #1: (No Response)

Reviewer #2: Dear Authors,

I have reviewed your manuscript titled "Cross-sectional study of the association of social relationship resources with Staphylococcus aureus colonization in naturally occurring social groups" and I am pleased to say that I found it to be a well-written and informative piece of research.

Your study sheds light on an important topic, and I believe that the findings will provide essential information for the scientific community. The results are presented in a clear and concise manner, and the methodology is sound. I particularly appreciated the thorough analysis of the data and the discussion of the potential implications of the results.

Overall, I commend you on your work and thank you for your contribution to the field. I wish you all the best in your future research endeavors.

Sincerely,

Dr. Umer

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

**********

PLoS One. 2023 Apr 13;18(4):e0284400. doi: 10.1371/journal.pone.0284400.r004

Author response to Decision Letter 1

24 Mar 2023

Please incorporate the following minor corrections so that the manuscript would be acceptable for publication.

1. First person pronouns have been used frequently, the manuscript should be written anonymously and use of first person must be very limited.

All first person language has been removed.

2. Inclusion and exclusion criteria has to be precisely mentioned.

We elaborated on the inclusion and exclusion criteria in the Method section on p. 8.

PLoS One. doi: 10.1371/journal.pone.0284400.r005

Decision Letter 2

Samiullah Khan

29 Mar 2023

Cross-sectional study of the association of social relationship resources with Staphylococcus aureus colonization in naturally occurring social groups along the US/Mexico border

PONE-D-23-00421R2

Dear Dr. Steven Barger,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Samiullah Khan, Ph. D

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

PLoS One. doi: 10.1371/journal.pone.0284400.r006

Acceptance letter

Samiullah Khan

4 Apr 2023

PONE-D-23-00421R2

Cross-sectional study of the association of social relationship resources with Staphylococcus aureus colonization in naturally occurring social groups along the US/Mexico border

Dear Dr. Barger:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Samiullah Khan

Academic Editor

PLOS ONE

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

S1 File. Raw data for the study.

(XLS)

Click here for additional data file.^{(351KB, xls)}

Attachment

Submitted filename: PONE-D-23-00421.docx

Click here for additional data file.^{(140.1KB, docx)}

Attachment

Submitted filename: Response to Reviewers.docx

Click here for additional data file.^{(244.7KB, docx)}

Data Availability Statement

All relevant data are within the paper and its Supporting Information files.

[pone.0284400.ref001] 1.Cohen S, Doyle WJ, Skoner DP, Rabin BS, Gwaltney JM Jr., Social ties and susceptibility to the common cold. JAMA. 1997;277: 1940–4. [PubMed] [Google Scholar]

[pone.0284400.ref002] 2.Edmunds WJ, Medley GF, O’Callaghan CJ. Social ties and susceptibility to the common cold. JAMA. 1997;278: 1231; author reply 2. doi: 10.1001/jama.278.15.1231b [DOI] [PubMed] [Google Scholar]

[pone.0284400.ref003] 3.Tong SYC, Davis JS, Eichenberger E, Holland TL, Fowler VG. Staphylococcus aureus infections: epidemiology, pathophysiology, clinical manifestations, and management. Clin Microbiol Rev. 2015;28: 603–61. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0284400.ref004] 4.Kourtis AP, Hatfield K, Baggs J, Mu Y, See I, Epson E, et al. Epidemiology and recent trends in methicillin-resistant and in methicillin-susceptible Staphylococcus aureus bloodstream infections—United States. MMWR. 2019;68: 214–9. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0284400.ref005] 5.Gorwitz RJ, Kruszon-Moran D, McAllister SK, McQuillan G, McDougal LK, Fosheim GE, et al. Changes in the prevalence of nasal colonization with Staphylococcus aureus in the United States, 2001–2004. J Infect Dis. 2008;197: 1226–34. [DOI] [PubMed] [Google Scholar]

[pone.0284400.ref006] 6.Russakoff B, Wood C, Lininger MR, Barger SD, Trotter RT, Maltinsky S, et al. A quantitative assessment of Staphylococcus aureus community carriage in Yuma, Arizona. J Infect Dis. 2022. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0284400.ref007] 7.Gualandi N, Mu Y, Bamberg WM, Dumyati G, Harrison LH, Lesher L, et al. Racial disparities in invasive methicillin-resistant Staphylococcus aureus infections, 2005–2014. Clin Infect Dis. 2018;67: 1175–81. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0284400.ref008] 8.von Eiff C, Becker K, Machka K, Stammer H, Peters G. Nasal carriage as a source of Staphylococcus aureus bacteremia. N Engl J Med. 2001;344: 11–6. [DOI] [PubMed] [Google Scholar]

[pone.0284400.ref009] 9.Perl TM, Cullen JJ, Wenzel RP, Zimmerman MB, Pfaller MA, Sheppard D, et al. Intranasal mupirocin to prevent postoperative Staphylococcus aureus infections. N Engl J Med. 2002;346: 1871–7. [DOI] [PubMed] [Google Scholar]

[pone.0284400.ref010] 10.Wertheim HF, Melles DC, Vos MC, van Leeuwen W, van Belkum A, Verbrugh HA, et al. The role of nasal carriage in Staphylococcus aureus infections. Lancet Infect Dis. 2005;5: 751–62. [DOI] [PubMed] [Google Scholar]

[pone.0284400.ref011] 11.Brissette I, Cohen S, Seeman TE. Measuring social integration and social networks. In: Cohen S, Underwood L, Gottlieb B, editors. Measuring and intervening in social support New York: Oxford University Press; 2000. p. 53–85. [Google Scholar]

[pone.0284400.ref012] 12.Berkman LF, Glass T, Brissette I, Seeman TE. From social integration to health: Durkheim in the new millennium. Soc Sci Med. 2000;51: 843–57. doi: 10.1016/s0277-9536(00)00065-4 [DOI] [PubMed] [Google Scholar]

[pone.0284400.ref013] 13.Barger SD. Social integration, social support and mortality in the US National Health Interview Survey. Psychosom Med. 2013;75: 510–7. doi: 10.1097/PSY.0b013e318292ad99 [DOI] [PubMed] [Google Scholar]

[pone.0284400.ref014] 14.Barger SD, Uchino BN. Racial and ethnic variation in the association of social integration with mortality: ten-year prospective population-based US study. Sci Rep. 2017;7: 43874. doi: 10.1038/srep43874 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0284400.ref015] 15.de Jong Gierveld J, Havens B. Cross-national comparisons of social isolation and loneliness: introduction and overview. Can J Aging. 2004;23: 109–13. doi: 10.1353/cja.2004.0021 [DOI] [PubMed] [Google Scholar]

[pone.0284400.ref016] 16.de Jong-Gierveld J. Developing and testing a model of loneliness. J Pers Soc Psychol. 1987;53: 119–28. doi: 10.1037//0022-3514.53.1.119 [DOI] [PubMed] [Google Scholar]

[pone.0284400.ref017] 17.Shankar A, McMunn A, Banks J, Steptoe A. Loneliness, social isolation, and behavioral and biological health indicators in older adults. Health Psychol. 2011;30: 377–85. doi: 10.1037/a0022826 [DOI] [PubMed] [Google Scholar]

[pone.0284400.ref018] 18.DeSalvo KB, Bloser N, Reynolds K, He J, Muntner P. Mortality prediction with a single general self-rated health question. A meta-analysis. J Gen Intern Med. 2006;21: 267–75. doi: 10.1111/j.1525-1497.2005.00291.x [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0284400.ref019] 19.Goldberg P, Gueguen A, Schmaus A, Nakache JP, Goldberg M. Longitudinal study of associations between perceived health status and self reported diseases in the French Gazel cohort. J Epidemiol Community Health. 2001;55: 233–8. doi: 10.1136/jech.55.4.233 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0284400.ref020] 20.Idler EL, Benyamini Y. Self-rated health and mortality: a review of twenty-seven community studies. J Health Soc Behav. 1997;38: 21–37. [PubMed] [Google Scholar]

[pone.0284400.ref021] 21.Barger SD, Cribbet MR, Muldoon MF. Participant-reported health status predicts cardiovascular and all-cause mortality independent of established and nontraditional biomarkers: evidence from a representative US sample. J Am Heart Assoc. 2016;5: e003741. doi: 10.1161/JAHA.116.003741 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0284400.ref022] 22.Haring R, Feng YS, Moock J, Volzke H, Dorr M, Nauck M, et al. Self-perceived quality of life predicts mortality risk better than a multi-biomarker panel, but the combination of both does best. BMC Med Res Methodol. 2011;11: 103. doi: 10.1186/1471-2288-11-103 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0284400.ref023] 23.Laugesen K, Baggesen LM, Schmidt SAJ, Glymour MM, Lasgaard M, Milstein A, et al. Social isolation and all-cause mortality: a population-based cohort study in Denmark. Sci Rep. 2018;8: 4731. doi: 10.1038/s41598-018-22963-w [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0284400.ref024] 24.Sirven N, Debrand T. Social participation and healthy ageing: An international comparison using SHARE data. Soc Sci Med. 2008;67: 2017–26. doi: 10.1016/j.socscimed.2008.09.056 [DOI] [PubMed] [Google Scholar]

[pone.0284400.ref025] 25.Gorman BK, Sivaganesan A. The role of social support and integration for understanding socioeconomic disparities in self-rated health and hypertension. Soc Sci Med. 2007;65: 958–75. doi: 10.1016/j.socscimed.2007.04.017 [DOI] [PubMed] [Google Scholar]

[pone.0284400.ref026] 26.Platt JR. Strong inference: certain systematic methods of scientific thinking may produce much more rapid progress than others. Science. 1964;146: 347–53. doi: 10.1126/science.146.3642.347 [DOI] [PubMed] [Google Scholar]

[pone.0284400.ref027] 27.Barger SD, Lininger MR, Trotter RT 2nd, Wayment HA, Mbegbu M, Kyman S, et al. Educational attainment and Staphylococcus aureus colonization in a Hispanic border community: testing fundamental cause theory. mSphere. 2020;5. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0284400.ref028] 28.Pearson T, Barger SD, Lininger M, Wayment H, Hepp C, Villa F, et al. Health disparities in Staphylococcus aureus transmission and carriage in a border region of the United States based on cultural differences in social relationships: protocol for a survey study. JMIR Res Protoc. 2019;8: e14853. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0284400.ref029] 29.Centers for Disease Control and Prevention. Behavioral Risk Factor Surveillance System, LLCP 2019 Codebook Report. 2020. Available from: https://www.cdc.gov/brfss/annual_data/2019/pdf/codebook19_llcp-v2-508.HTML.

[pone.0284400.ref030] 30.National Center for Health Statistics, Division of Health Interview Statistics. 2001 National Health Interview Survey (NHIS) public use data release: Sample adult file. Hyattsville, Maryland 2003. Available from: https://ftp.cdc.gov/pub/Health_Statistics/NCHS/Survey_Questionnaires/NHIS/2001/qsamadlt.pdf.

[pone.0284400.ref031] 31.Barger SD, Donoho CJ, Wayment HA. The relative contributions of race/ethnicity, socioeconomic status, health, and social relationships to life satisfaction in the United States. Qual Life Res. 2009;18: 179–89. doi: 10.1007/s11136-008-9426-2 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0284400.ref032] 32.McGinty EE, Presskreischer R, Han H, Barry CL. Psychological distress and loneliness reported by US adults in 2018 and April 2020. JAMA. 2020;324: 93–4. doi: 10.1001/jama.2020.9740 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0284400.ref033] 33.Barger SD, Messerli-Bürgy N, Barth J. Social relationship correlates of major depressive disorder and depressive symptoms in Switzerland: nationally representative cross sectional study. BMC Public Health. 2014;14: 273. doi: 10.1186/1471-2458-14-273 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0284400.ref034] 34.Sjoberg L, Ostling S, Falk H, Sundh V, Waern M, Skoog I. Secular changes in the relation between social factors and depression: a study of two birth cohorts of Swedish septuagenarians followed for 5 years. J Affect Disord. 2013;150: 245–52. doi: 10.1016/j.jad.2013.04.002 [DOI] [PubMed] [Google Scholar]

[pone.0284400.ref035] 35.Pressman SD, Cohen S, Miller GE, Barkin A, Rabin BS, Treanor JJ. Loneliness, social network size, and immune response to influenza vaccination in college freshmen. Health Psychol. 2005;24: 297–306. doi: 10.1037/0278-6133.24.3.297 [DOI] [PubMed] [Google Scholar]

[pone.0284400.ref036] 36.Wood C, Sahl J, Maltinsky S, Coyne B, Russakoff B, Yague DP, et al. SaQuant: a real-time PCR assay for quantitative assessment of Staphylococcus aureus. BMC Microbiol. 2021;21: 174. doi: 10.1186/s12866-021-02247-6 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0284400.ref037] 37.Panisello Yague D, Mihaljevic J, Mbegbu M, Wood CV, Hepp C, Kyman S, et al. Survival of Staphylococcus aureus on sampling swabs stored at different temperatures. J Appl Microbiol. 2021. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0284400.ref038] 38.Pearson T, Hepp C, Trotter RT 2nd, Mbegbu M, Russakoff B, Panisello Yague D, et al. Genome sequences of community carriage strains of Staphylococcus aureus from Yuma, Arizona. Microbiol Resour Announc. 2021;10: e0044921. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0284400.ref039] 39.Long JS, Freese J. Regression models for categorical outcomes using Stata. 2nd ed. College Station, TX: Stata Press; 2003. [Google Scholar]

[pone.0284400.ref040] 40.Zou G. A modified poisson regression approach to prospective studies with binary data. Am J Epidemiol. 2004;159: 702–6. doi: 10.1093/aje/kwh090 [DOI] [PubMed] [Google Scholar]

[pone.0284400.ref041] 41.Norton EC, Dowd BE, Maciejewski ML. Odds ratios-current best practice and use. JAMA. 2018;320: 84–5. doi: 10.1001/jama.2018.6971 [DOI] [PubMed] [Google Scholar]

[pone.0284400.ref042] 42.Lininger MR, Root HJ, Camplain R, Barger SD. Describing the appropriate use and interpretation of odds and risk ratios. Res Sports Med. 2022: forthcoming. doi: 10.1080/15438627.2022.2132861 [DOI] [PubMed] [Google Scholar]

[pone.0284400.ref043] 43.Norton EC, Dowd BE. Log odds and the Interpretation of logit models. Health Serv Res. 2018;53: 859–78. doi: 10.1111/1475-6773.12712 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0284400.ref044] 44.Petersen MR, Deddens JA. A comparison of two methods for estimating prevalence ratios. BMC Med Res Methodol. 2008;8: 9. doi: 10.1186/1471-2288-8-9 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0284400.ref045] 45.Holt-Lunstad J, Smith TB, Baker M, Harris T, Stephenson D. Loneliness and social isolation as risk factors for mortality: a meta-analytic review. Perspect Psychol Sci. 2015;10: 227–37. doi: 10.1177/1745691614568352 [DOI] [PubMed] [Google Scholar]

[pone.0284400.ref046] 46.Benyamini Y, Idler EL. Community studies reporting association between self-rated health and mortality: additional studies, 1995 to 1998. Res Aging. 1999;21: 392–401. [Google Scholar]

[pone.0284400.ref047] 47.Knox J, Uhlemann AC, Lowy FD. Stopping household methicillin-resistant Staphylococcus aureus transmission and recurrent infections: an unmet challenge. Clin Infect Dis. 2021;73: e4578–e80. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0284400.ref048] 48.Ng W, Faheem A, McGeer A, Simor AE, Gelosia A, Willey BM, et al. Community- and healthcare-associated methicillin-resistant Staphylococcus aureus strains: An investigation into household transmission, risk factors, and environmental contamination. Infect Control Hosp Epidemiol. 2017;38: 61–7. [DOI] [PubMed] [Google Scholar]

[pone.0284400.ref049] 49.Shankar N, Chow ALP, Oon J, Hsu LY, Ang B, Pang J, et al. The epidemiology and transmission of methicillin-resistant Staphylococcus aureus in the community in Singapore: study protocol for a longitudinal household study. BMC Infect Dis. 2017;17: 678. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0284400.ref050] 50.Knox J, Uhlemann AC, Lowy FD. Staphylococcus aureus infections: transmission within households and the community. Trends Microbiol. 2015;23: 437–44. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0284400.ref051] 51.Noppert GA, Kubale JT. Incorporating social environment data in infectious disease research. Lancet Public Health. 2023;8: e88–e9. doi: 10.1016/S2468-2667(23)00005-1 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0284400.ref052] 52.Popovich KJ, Aroutcheva A, Hota B, Beavis KG, Hayden MK, Weinstein RA. Anatomic sites of colonization with community-associated methicillin-resistant Staphylococcus aureus. Infect Control Hosp Epidemiol. 2014;35: 1192–4. [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0284400.ref053] 53.Coyle CE, Dugan E. Social isolation, loneliness and health among older adults. J Aging Health. 2012;24: 1346–63. [DOI] [PubMed] [Google Scholar]

[pone.0284400.ref054] 54.Elovainio M, Komulainen K, Sipila PN, Pulkki-Raback L, Cachon Alonso L, Pentti J, et al. Association of social isolation and loneliness with risk of incident hospital-treated infections: an analysis of data from the UK Biobank and Finnish Health and Social Support studies. Lancet Public Health. 2023;8: e109–e18. doi: 10.1016/S2468-2667(22)00253-5 [DOI] [PMC free article] [PubMed] [Google Scholar]

[pone.0284400.ref055] 55.Ki V, Rotstein C. Bacterial skin and soft tissue infections in adults: A review of their epidemiology, pathogenesis, diagnosis, treatment and site of care. Can J Infect Dis Med Microbiol. 2008;19: 173–84. doi: 10.1155/2008/846453 [DOI] [PMC free article] [PubMed] [Google Scholar]

PERMALINK

Cross-sectional study of the association of social relationship resources with Staphylococcus aureus colonization in naturally occurring social groups along the US/Mexico border

Steven D Barger

Monica R Lininger

Robert T Trotter II

Mimi Mbegbu

Shari Kyman

Kara Tucker-Morgan

Colin Wood

Briana Coyne

Benjamin Russakoff

Kathya Ceniceros

Cristina Padilla

Sara Maltinsky

Talima Pearson

Roles

Abstract

Introduction

Materials and methods

Study overview

Participants

Fig 1. STROBE flow diagram.

Social relationship assessments

Social network index

Social integration and loneliness

Detection of S. aureus

Data reduction and analysis

Table 1. Sample sociodemographic characteristics.

Results

Table 2. Correlations among social relationship variables, self-rated health and colonization with S. aureus.

Social relationships and self-rated health

Table 3. Coefficients regressing self-rated health on social relationship variables.

Colonization with S. aureus

Social relationships and colonization with S. aureus

Table 4. Incidence rate ratios (IRR) regressing S. aureus colonization on individual social relationship variables.

Discussion

Conclusions

Supporting information

Acknowledgments

Abbreviations

Data Availability

Funding Statement

References

Decision Letter 0

Samiullah Khan

Roles

Author response to Decision Letter 0

Decision Letter 1

Samiullah Khan

Roles

Author response to Decision Letter 1

Decision Letter 2

Samiullah Khan

Roles

Acceptance letter

Samiullah Khan

Roles

Associated Data

Supplementary Materials

Data Availability Statement

ACTIONS

PERMALINK

RESOURCES

Similar articles

Cited by other articles

Links to NCBI Databases