The Relation of Nasopharyngeal Colonization by Streptococcus pneumoniae in Comorbid Adults with Pneumonia and Unfavorable Outcomes in a Low-Middle Income Country

The Relation of Nasopharyngeal Colonization by Streptococcus pneumoniae in Comorbid Adults with Pneumonia and Unfavorable Outcomes in a Low-Middle Income Country | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The Relation of Nasopharyngeal Colonization by Streptococcus pneumoniae in Comorbid Adults with Pneumonia and Unfavorable Outcomes in a Low-Middle Income Country Juan Olivella-Gomez, Julián Lozada, Lina Méndez-Castillo, André Emilio Viñán Garcés, and 16 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4294799/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose : Streptococcus pneumoniae (Spn ) is the primary bacterial cause of lower respiratory tract infections (LRTI) globally, particularly impacting older adults and children. While Spn colonization in children is linked to LRTI, its prevalence and consequences in adults with comorbidities remains uncertain. This study aims to provide novel data in that regard. Methods : This is a prospective study of outpatient adults with chronic diseases. Data on demographics, vaccination, and clinical history was gathered. Nasopharyngeal aspirate samples were examined for Spn colonization using traditional cultures and PCR. Patients were followed for 18 months, with colonization prevalence calculated and factors influencing colonization and its impact on clinical outcomes analyzed through logistic regressions. Results : 810 patients were enrolled, with 10.1% (82/810) identified as colonized. The mean (SD) age was 62 years (±15), and 48.6% (394/810) were female. Major comorbidities included hypertension (52.2% [423/810]), cardiac conditions (31.1% [252/810]), and chronic kidney disease (17.4% [141/810]). Among all, 31.6% (256/810) received the influenza vaccine in the previous year, and 10.7% (87/810) received anti- Spn vaccines. Chronic kidney disease (OR 95% CI; 2.48 [1.01-6.15], p=0.04) and chronic cardiac diseases (OR 95% CI; 1.62 [0.99-2.66], p=0.05) were independently associated with Spn colonization. However, colonization did not increase the risk of LRTI (OR 95%CI; 0.64 [0.14-2.79], p=0.55) or unfavorable outcomes (OR 95% CI;1.17 [0.14-2.79], p=0.54) during follow-up. Conclusions : Chronic kidney and cardiac diseases are independently associated with Spn colonization, underscoring the importance of vaccination in this population. Spn colonization was not associated with LRTI/unfavorable outcomes in adult patients with chronic comorbidities. Figures Figure 1 Figure 2 Figure 3 Introduction Lower respiratory tract infections (LRTI) are the leading infectious causes of mortality worldwide [1]. According to the Global Burden of Disease (GBD), LRTI etiology is most frequently attributed to microorganisms such as Streptococcus pneumoniae , Haemophilus influenzae type b (Hib), influenza viruses, and respiratory syncytial virus (RSV), among others [2]. S. pneumoniae stands out as the principal contributor to morbidity and mortality resulting from infectious diseases across the globe [3]. Notably, the highest burden of pneumococcal disease (PD) has been documented in the most vulnerable populations, namely, at the extremes of age and those with chronic comorbid conditions [4]. Several risk factors have been associated with PD in adults, including advanced age, chronic medical comorbidities, and immunocompromising conditions [5, 6]. In contrast, others have been postulated in children, such as nasopharyngeal pneumococcal colonization (NPC) [7]. Nasopharyngeal carriage is considered the first step toward invasive pneumococcal disease (IPD) in children [7]. This colonization is possible due to several mechanisms, including the evasion of mucus entrapment by capsular polysaccharide, biofilm formation, expression of adhesion proteins, inhibition of complement proteins, and release of bacteriocins to mediate competition with local microbiota [8]. The systemic repercussions of NPC have been explored in the pediatric population [9], and a relationship with the development of acute respiratory infections has been established, especially when a high pneumococcal carriage density was present [10]. In adults, several risk factors for colonization have been described, such as smoking, living with children, and residence in a nursing home [11]; however, the relationship with LRTI is still unclear in adults. This study aims to determine the prevalence of Spn NPC and to evaluate the relationship between NPC and the development of LRTIs or other important clinical outcomes (i.e., number of hospitalizations or mortality due to infectious diseases) in adult patients with comorbidities. Furthermore, it explores factors associated with NPC colonization, assesses the adherence of patients to anti- Spn vaccination based on current local guidelines, and thus identifying specific patient subgroups that may derive substantial benefits from inclusion in vaccination programs. Materials And Methods This prospective multicenter cohort study in adult patients with chronic diseases from four outpatient clinics in Bogotá – Colombia. The protocol and informed consent were developed by the Translational Science in Infectious Diseases and Critical Care Medicine (TSID-CCM) research group from the Universidad de La Sabana. These were reviewed and authorized by the Institutional Review Board/Independent Ethics Committee (IRB/EC) of the participating institutions. Ethical supervision ensured informed consent was obtained from all study participants or their authorized representatives. Inclusion criteria included individuals aged 18 years and older with at least one chronic disease that were actively attending one of the four participating centers between December 2020 and March 2022. Definitions of comorbidities are detailed in supplementary material 1. The exclusion criteria included patients with evidence of respiratory symptoms (e.g., rhinorrhea, fever, or expectoration) or diagnosis of community-acquired pneumonia (CAP) during the prior to 90 days according to the criteria of the American Thoracic Association (ATS) - Infectious Diseases Society of America (IDSA) [12]. Also, subjects admitted to the hospital during the previous 7 days of enrollment or limited to providing biological-type samples were also excluded from the study. Definitions NPC was defined as the identification of Spn by either conventional culture method further confirmed through matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) or sigmoidal curve amplification of both pneumolysin (ply) and autolysin (lytA) genes by quantitative polymerase chain reaction (qPCR) in nasopharyngeal aspirates (NPA). Furthermore, CAP diagnosis was determined using the definition of IDSA/ATS guidelines during the follow-up [12]. The vaccination scheme was evaluated based on the specific conditions of the patient and the indications based on the local guidelines for anti- Spn vaccination [13]. Finally, the composite variable termed “unfavorable outcome” was constructed of patients who developed CAP, were hospitalized due to an infectious cause, whether by Spn or other microorganisms or that succumbed to pneumonia or another infectious cause at any point during the follow-up period. Data Collection Data collection was carried out by a dedicated research assistant, who gathered sociodemographic details of medical history, including comorbidities, living conditions, and lifestyle habits. Participants were also required to provide a verifiable vaccination record or based on medical records. The data collection process used an Electronic Case Report Form (eCRF) developed within the Research Electronic Data Capture (REDCap) platform (version 8.11.11 provided by Vanderbilt University, Nashville, Tenn.), hosted by Universidad de Sabana. Follow-up data was collected by phone calls at 6, 12, and 18 months after the date of enrollment. Sample Collection For all patients enrolled in the study after signing informed consent, trained nursing staff collected NPA samples with an 8 mm nelaton probe (Medex, INVIMA 2008DM - 0001689 R2, Colombia) and 8-10 cc rinsing infusion of physiological saline solution (PSS) of sodium chloride 0. 9% (Baxter, Viaflex) at 10 - 15 cm in the posterior nostril of each participant according to the guidelines of the WHO (World Health Organization) Pneumococcal Carriage Working Group in 2013 [14]. Laboratory procedures In the laboratory, 100 𝜇L of nasopharyngeal aspirate (NPA) was immediately inoculated on blood agar and incubated at 37°C +/- 2°C for 24-48 hours in 5% CO2. Alpha-hemolytic colonies were selected, underwent optochin sensitivity testing, and sensitive strains were identified using (MALDI-TOF) mass spectrometry. "Suspected cases" were defined as colonization with Spn when alpha-hemolytic colonies showed optochin sensitivity > 14 mm [15]. "Confirmed cases" had MALDI-TOF scores > 1.8 [16]. Additionally, a qPCR approach targeting ply and lytA genes was employed, adhering to specific criteria for pneumococcal colonization identification, including Ct < 35 (17-19] and characteristic melt curve profiles ( Figure 2 ) [20]. Information regarding conventional culture, primer selection, run cycle, and standard curve identification for ply and lytA gene identification and specific criteria for colonization identification can be found in the online supplement. ( Supplementary material 3 ) Follow-up period Throughout the follow-up period, phone interviews were systematically conducted with each patient at 6, 12, and 18 months from the enrollment date unless their demise or dissent of participation was previously known. These interviews aimed to gather information on instances of hospitalization, including the cause and duration, and to inquire about the development of pneumonia. If pneumonia occurred, patients were asked to provide their medical records. Then, a detailed chart review assessed the identified etiology and details of antibiotic use, including the duration of therapy and clinical outcomes. In cases where the patient had passed away, details such as the date and cause of death were meticulously recorded. Vaccination status was updated if the patient had been vaccinated during the study period. The inquiry spanned the last 6 months preceding the call. Statistical analysis A descriptive analysis was developed with measures of central tendency (mean or median) and dispersion, standard deviation (SD), and interquartile range (IQR) depending on normality distribution, respectively identified by the Shapiro-Wilk test for quantitative variables and frequencies with percentages for qualitative variables. Pneumococcal NPC period prevalence was calculated as a proportion of confirmed cases over the total number of subjects included in the study over the period of recruitment. Demographic variables and comorbidities were compared between the colonized and non-colonized groups to determine heterogeneity by applying the chi-square and Fisher's exact tests for categorical variables; on the other hand, Student's T-test or the Mann-Whitney U test was employed to assess continuous variables, depending on their distribution. A multivariate logistic regression model was carried out to identify factors associated with colonization, adjusting for age to incorporate demographic details upon admission. The stepwise logistic regression method incorporated variables with a significance level at or below 0.20 in the preceding univariate analysis. Additionally, to investigate the impact of colonization on adverse outcomes, a composite variable named unfavorable outcomes, as described above, was considered across the 18-month follow-up period. This subsequent model was adjusted for age, vaccination status, and renal replacement therapy; this adjustment addressed potential selection bias given considerable recruitment from patients undergoing renal replacement therapy. Odds ratios (OR) and a 95% confidence interval (95% CI) were computed using the exponential values derived from the coefficients of the final model. All statistical analyses were performed using IBM SPSS Statistics for Mac, version 22.0, Armonk, NY: I.B.M. Corp. Results Between December 2020 and March 2022, 810 patients were enrolled, with 82 (10.1%) identified as colonized through conventional culture and/or the qPCR method. In the overall cohort, the average age of the study population was 62 years, with a standard deviation of ± 15 years, and females represented 48.6% (394/810) of the cohort. The predominant comorbidity among the studied population was hypertension (52% [423/810]), followed by cardiac conditions (31% [252/810]) and chronic kidney disease (CKD) (17.4% [141/810]); all the other comorbid conditions are presented in Table 1 . Regarding environmental factors, 13.1% (106/810) of the patients lived with small children, and 14.4% (117/810) were smokers. Other detailed demographic and clinical characteristics for the overall cohort and stratified by Spn colonization are provided in (Supplementary Material 2) . Regarding vaccination, 31.6% (256/810) of patients had received the influenza vaccine during the prior year, while 10.7% (87/810) had been administered a version of the anti -Spn vaccine before study enrollment. Among those who received the pneumococcal vaccine, 50% (44/87) were administered the PPSV-23, 11.4% (10/87) received PCV-13, and 3.4% (3/87) were given the PSSV+PCV scheme. Notably, 33.3% (29/87) of individuals could not specify the type of pneumococcal vaccine they received but were aware of having received it. Only 1.1% (1/87) reported receiving PCV-10. Further details regarding vaccination within each subgroup based on local guidelines can be found in ( Table 2 ). Over the 18-month follow-up period, 3.5% (29/810) of the cohort developed pneumonia, comprising 12 cases at 6 months, 13 at 12 months, and 4 cases at 18 months. In total, 20.2% (164/810) of participants were hospitalized for any cause during the follow-up, resulting in 248 admissions: 76 at 6 months, 89 at 12 months, and 83 at 18 months. Among these hospitalizations, 46 were attributed to infectious causes at 6 months, 56 at 12 months, and 40 at 18 months, contributing to 142 hospitalizations included in the composite outcome variable of unfavorable outcome. The mortality rate was 4.1% (34/810) at 6 months, 1.7% (13/776) during the following 6 months, and reached 1.4% (11/763) during the last 6 months for a total of 7.2% (58/810) during the entire 18-month follow-up period. Additional insights into the observed outcomes at each time point are visually presented in ( Figure 1 ), providing a comprehensive overview of the cohort's trajectory over the specified period. Outcomes The Spn NPC period prevalence was determined to be 10.1% (82/810) during the patient observation period. Over the 18-month follow-up, 28.3% (230/810) of patients developed any of the three considered outcomes within the unfavorable outcome variable. A multivariate logistic regression was conducted to explore the correlation between comorbidities and Spn colonization. In this analysis, chronic kidney disease was identified as a risk factor for colonization, showing an odds ratio (OR, [95% CI]) of 2.48 (1.01 – 6.15), p = 0.04. Similarly, cardiac diseases presented a statistically significant risk factor, albeit crossing the confidence interval, with an OR of 1.62 (0.99 - 2.66), p = 0.05. Although significant in the univariate analysis, chronic hepatic disease did not demonstrate a correlation in this multivariate analysis. Details on specific outcomes for the univariate and multivariate analysis can be found in ( Figure 3) . Hosmer-Lemeshow test for binary logistic regression models demonstrated the goodness-of-fit test (p=0.703). Similarly, a multivariate binary logistic regression analysis was conducted to examine whether colonization by S. pneumoniae predisposed patients to develop an unfavorable outcome, as previously defined. This analysis, adjusted for age, vaccination status, and the need for renal replacement therapy, revealed that colonization by either traditional culture or qPCR showed no statistically significant correlation with unfavorable outcomes (OR [95% CI]) (1.17 [0.69 - 1.98], p = 0.54). Further information regarding both univariate and multivariate analyses can be found in the online supplement ( Supplementary material 4-5 ). Moreover, a sub-analysis specifically for LTRI development showed that colonization was not a risk factor for LTRI development taking into account the bias that the low number of events represent (OR [95% CI]) (0.64 [0.14 - 2.78], p = 0.55) ( Supplementary material 6 ). Age was demonstrated to be independently associated with unfavorable outcomes in the multivariate analysis (1.81 [1.28 - 2.58], p < 0.01). As expected, the need for renal replacement therapy emerged as a significant contributor to unfavorable outcomes in the multivariate analysis (5.10 [3.43 - 7.58], p < 0.01). Specific outcomes from the multivariate analysis are detailed in ( Figure 3B) , and the Hosmer-Lemeshow test for binary logistic regression models demonstrated the goodness-of-fit test ( p =0.548). Discussion This prospective study performed a comprehensive clinical and microbiological assessment of patients with comorbid conditions to determine the prevalence of nasopharyngeal colonization and its impact on clinical outcomes during an 18-month period. We identified a low rate of pneumococcal colonization among Colombian, a low-middle income country, comorbid adults. Moreover, we found that Spn frequently colonized patients with CKD and cardiac diseasesand that these comorbid conditions were independently associated with nasopharyngeal colonization by Spn . Finally, we found no correlation between Spn colonization and the development of either LRTIs, a higher number of hospitalizations, or higher mortality rates due to related infectious causes. The reported Spn colonization of 10.1% [82/810) aligns with findings from prior studies in adults, which have reported a prevalence range of 1-10% [15, 16]. In a recent meta-analysis performed by our group, we found an overall prevalence of 6%, and a subgroup analysis prevalence of 2% for adults only [21]. However, the majority of these studies were performed in high-income countries, in healthy volunteers, or in specific groups of comorbidities [e.g., HIV patients). For instance, Carvalho et al. performed a study in Kenya in healthy participants, reporting a rate of 6.4% [n=450) in adults >18 years , and Palmu et al. reported a 5,23% prevalence in healthy adults >65 years [m=592) [23]. Conversely, comorbidity-focused studies, such as those published by Heinsbroek et al. and Dayie et al. in Malawi and Ghana, show higher rates [21.3%, 10.0%) in adults with HIV and sickle cell anemia, respectively [24, 25]. Studies by Milucky et al. and Roca-Oporto et al. undertaken in developed nations like the US and Spain report lower rates (1.8% to 5,6%) in individuals with solid organ transplants and chronic diseases [26, 27]. Notably, patients with influenza-related respiratory symptoms exhibit rates as high as 31% [28]. Therefore, our findings are novel because they assessed the nasopharyngeal colonization by Spn in a broader cohort of patients with multiple chronic comorbid conditions in a lower-income country, using traditional cultures and rtPCR-based techniques, making these results more generalizable. Interestingly, this real-world study found a low anti- Spn vaccination rate among adults with comorbid conditions. Also, we found a low colonization rate despite suboptimal vaccination rates per local guidelines. In contrast, prior literature has shown that before the introduction of the conjugate vaccine in state schedules, Nicoletti et al . and Blossom et al. identified in Brazil and Uganda high proportions of culture-based colonization in adult HIV patients, 16% and 18%, respectively [29, 30], and in the U.S., Becker-Dreps et al. found in older adults with general comorbidity a 1.9% colonization rate [31]. Following the incorporation of conjugate vaccines (PCV 7, 10, 13, 15, and 20), Drayss et al. found in adults > 65 years from geriatric homes in Germany with low comorbidity levels, colonization rates of 0% [32]. Notably, our results highlight the need for more robust vaccination campaigns in adults with chronic comorbid conditions in countries with limited resources, as it is evident that solid vaccination campaigns could reduce IPD in adults [33]. Van Hoek and Pekuz et al. studies have indicated a relationship between CKD and IPD [34, 35]. Also, some studies have highlighted better outcomes and survival rates in vaccinated patients with comorbid conditions [36, 37]. However, limited research explores CKD's link to colonization. Cardiovascular disease (CVD) and heart failure are frequently associated with pneumococcal disease [38-40], but their association with colonization risk remains uncertain across studies [41]. Thus, our finding that CKD and chronic cardiac diseases are independently associated with nasopharyngeal Spn- colonization highlights the importance of vaccination in these groups of patients. Finally, we did not find an association between Spn colonization and the development of any of the three unfavorable outcomes, which contradicts the currently available data on children. This finding is novel as, to our knowledge, this study is the first study exploring this relationship in adults with comorbid conditions. One possible explanation for our findings and how they differ from what has been previously reported in children is that adults have, as a result of prior exposure events to Spn , generated an adaptive immune response to Spn proteins, which would confer broad protection from disease caused by all serotypes of Spn . Alternatively, during childhood, these individuals were colonized by versions of Spn that carry capsule types most frequently associated with disease, and now, due to the production of antibodies to these capsule types, they are more likely to be colonized by strains not as capable of causing severe infection. Therefore, further studies are needed to understand the etiology of LRTI and unfordable outcomes in patients with comorbid conditions. Our study has some limitations that should be mentioned. First, our cohort size is relatively small, potentially impacting the ability to draw statistically significant associations. However, the study was powered to identify statistical differences, and more importantly, to the best of our knowledge, this is the first study assessing nasopharyngeal colonization in adults with comorbidities, rendering our findings applicable to a significant demographic subset. Second, we found a low prevalence of pneumococcal colonization that could be attributed to the inherent difficulty in culturing Spn . Nevertheless, the study employed molecular tests to augment the likelihood of successful isolations, enhancing the precision of our analysis. Furthermore, our study overlapped with the COVID-19 pandemic, which may have impacted social dynamics, underestimating the real behavior of the colonization phenomena [42]. In conclusion, this novel study reinforces existing evidence that comorbidities such as CKD and cardiac diseases increase susceptibility to pneumococcal colonization. These findings underscore the imperative need for vaccination in this population. Vaccination rates, particularly for pneumococcal vaccines, were suboptimal, highlighting the urge to implement adherence to vaccination guidelines. Finally, we found that nasopharyngeal colonization by Spn was not associated with unfavorable outcomes in this population, including the development of LRTI. There is a need for further research to understand the complex interactions between colonization, comorbidities, and clinical outcomes. Declarations Statements & Declarations Funding : This project was funded by M.S.D. Colombia, a subsidiary of Merck & Co., Inc., RAHWAY, NJ, USA and Universidad de La Sabana grant number (MED-285-2020) L.F.R. Competing Interests Potential Conflict of Interest: All authors have no conflict of interest. Disclosure Statement: The authors report there are no competing interests to declare. Author Contributions : Conceptualization: J.L., J.O.G., L.F.R.; Data curation: J.L., J.O.G., L.M.C., A.E.V.G., V.E., E.D.I.P., C.C.S.M., I.G.B., L.D.V., A.M.C., L.F.R.; Formal analysis: J.L., J.O.G., L.M.C., Y.V.F., A.A.G., V.E., E.D.I.P., C.C.S.M., L.F.R.; Funding acquisition: L.F.R.; Investigation: J.L., L.M.C., Y.V.F., A.E.V.G., V.E., A.A.G., E.D.I.P., D.F.J., L.D.V., G.P.R.C., J.A.R.O., L.F.R.; Methodology: J.L., J.O.G., Y.V.F., A.A.G., V.E., D.F.J., J.P.S., D.F.J., L.F.R.; Project administration: J.L., E.D.I.P., C.C.S.M., A.M.C., L.F.R.; Software: J.L., C.C.S.M., L.F.R.; Supervision: A.A.G., A.M.C., L.F.R.; Validation: J.L., Y.V.F., A.E.V.G., VE, E.D.I.P., C.C.S.M., I.G.B., G.P.R.C., J.A.R.O., L.F.R.; Visualization: J.L., J.O.G., L.M.C., A.E.V.G., VE, E.D.I.P., C.C.S.M., A.M.C., L.F.R.; Roles/Writing – original draft: J.L., J.O.G., L.M.C., E.D.I.P., C.C.S.M., A.E.V.G., VE, A.A.G., L.F.R.; and Writing – review & editing: J.L., J.O.G., L.M.C., E.D.I.P., C.C.S.M., I.G.B., A.E.V.G., VE, A.A.G., L.F.R. 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Scand J Infect Dis. 2012;44(6):433-8. https://doi.org/10.3109/00365548.2011.652162 Heinsbroek E, Tafatatha T, Phiri A, Ngwira B, Crampin AC, Read JM, et al. Persisting high prevalence of pneumococcal carriage among HIV-infected adults receiving antiretroviral therapy in Malawi: a cohort study. Aids. 2015;29(14):1837-44. https://doi.org/10.1097/Qad.0000000000000755 Dayie N, Tetteh-Ocloo G, Labi AK, Olayemi E, Slotved HC, Lartey M, et al. Pneumococcal carriage among sickle cell disease patients in Accra, Ghana: Risk factors, serotypes and antibiotic resistance. PLoS One. 2018;13(11):e0206728. https://doi.org/10.1371/journal.pone.0206728 Milucky J, Carvalho MG, Rouphael N, Bennett NM, Talbot HK, Harrison LH, et al. Streptococcus pneumoniae colonization after introduction of 13-valent pneumococcal conjugate vaccine for US adults 65 years of age and older, 2015-2016. Vaccine. 2019;37(8):1094-100. https://doi.org/10.1016/j.vaccine.2018.12.075 Roca-Oporto C, Cebrero-Cangueiro T, Gil-Marques ML, Labrador-Herrera G, Smani Y, Gonzalez-Roncero FM, et al. Prevalence and clinical impact of Streptococcus pneumoniae nasopharyngeal carriage in solid organ transplant recipients. BMC Infect Dis. 2019;19(1):697. https://doi.org/10.1186/s12879-019-4321-8 Krone CL, Wyllie AL, van Beek J, Rots NY, Oja AE, Chu ML, et al. Carriage of Streptococcus pneumoniae in aged adults with influenza-like-illness. PLoS One. 2015;10(3):e0119875. https://doi.org/10.1371/journal.pone.0119875 Nicoletti C, Brandileone MCC, Guerra MLS, Levin AS. Prevalence, serotypes, and risk factors for pneumococcal carriage among HIV-infected adults. Diagn Micr Infec Dis. 2007;57(3):259-65. https://doi.org/10.1016/j.diagmicrobio.2006.08.021 Blossom DB, Namayanja-Kaye G, Nankya-Mutyoba J, Mukasa JB, Bakka H, Rwambuya S, et al. Oropharyngeal colonization by among HIV-infected adults in Uganda:: assessing prevalence and antimicrobial susceptibility. International Journal of Infectious Diseases. 2006;10(6):458-64. https://doi.org/10.1016/j.ijid.2006.05.010 Becker-Dreps S, Kistler CE, Ward K, Killeya-Jones LA, Better OM, Weber DJ, et al. Pneumococcal Carriage and Vaccine Coverage in Retirement Community Residents. J Am Geriatr Soc. 2015;63(10):2094-8. https://doi.org/10.1111/jgs.13651 Drayss M, Claus H, Hubert K, Thiel K, Berger A, Sing A, et al. Asymptomatic carriage of Neisseria meningitidis, Haemophilus influenzae, Streptococcus pneumoniae, Group A Streptococcus and Staphylococcus aureus among adults aged 65 years and older. PLoS One. 2019;14(2):e0212052. https://doi.org/10.1371/journal.pone.0212052 Bonten MJ, Huijts SM, Bolkenbaas M, Webber C, Patterson S, Gault S, et al. Polysaccharide conjugate vaccine against pneumococcal pneumonia in adults. N Engl J Med. 2015;372(12):1114-25. https://doi.org/10.1056/NEJMoa1408544 van Hoek AJ, Andrews N, Waight PA, Stowe J, Gates P, George R, et al. The effect of underlying clinical conditions on the risk of developing invasive pneumococcal disease in England. J Infect. 2012;65(1):17-24. https://doi.org/10.1016/j.jinf.2012.02.017 Pekuz S, Soysal A, Akkoc G, Atici S, Yakut N, Gelmez GA, et al. Prevalence of Nasopharyngeal Carriage, Serotype Distribution, and Antimicrobial Resistance of Streptococcus pneumoniae among Children with Chronic Diseases. Jpn J Infect Dis. 2019;72(1):7-13. https://doi.org/10.7883/yoken.JJID.2017.410 Bond TC, Spaulding AC, Krisher J, McClellan W. Mortality of Dialysis Patients According to Influenza and Pneumococcal Vaccination Status. Am J Kidney Dis. 2012;60(6):959-65. https://doi.org/10.1053/j.ajkd.2012.04.018 Gilbertson DT, Guo HF, Arneson TJ, Collins AJ. The association of pneumococcal vaccination with hospitalization and mortality in hemodialysis patients. Nephrol Dial Transpl. 2011;26(9):2934-9. https://doi.org/10.1093/ndt/gfq853 Feldman C, Anderson R. Recent advances in our understanding of Streptococcus pneumoniae infection. F1000Prime Rep. 2014;6:82. https://doi.org/10.12703/P6-82 Corrales-Medina VF, Musher DM, Shachkina S, Chirinos JA. Acute pneumonia and the cardiovascular system. Lancet. 2013;381(9865):496-505. https://doi.org/10.1016/S0140-6736(12)61266-5 Viasus D, Garcia-Vidal C, Manresa F, Dorca J, Gudiol F, Carratala J. Risk stratification and prognosis of acute cardiac events in hospitalized adults with community-acquired pneumonia. J Infect. 2013;66(1):27-33. https://doi.org/10.1016/j.jinf.2012.09.003 Branche AR, Yang H, Java J, Holden-Wiltse J, Topham DJ, Peasley M, et al. Effect of prior vaccination on carriage rates of Streptococcus pneumoniae in older adults: A longitudinal surveillance study. Vaccine. 2018;36(29):4304-10. vhttps://doi.org/10.1016/j.vaccine.2018.05.107 Facciola A, Lagana A, Genovese G, Romeo B, Sidoti S, D'Andrea G, et al. Impact of the COVID-19 pandemic on the infectious disease epidemiology. J Prev Med Hyg. 2023;64(3):E274-E82. https://doi.org/10.15167/2421-4248/jpmh2023.64.3.2904 Tables Table 1. Distribution of comorbidities in Streptococcus pneumoniae ( Spn ) colonized and no Spn colonized patients. Total patients sampled n=810 No Spn colonized n=728 Spn colonized n=82 Characteristic Age mean, S.D. 62±15 62±15 64±15 Gender female, n (%) 394 (48,6) 357 (49,0) 37 (45,1) Health Care Worker, n (%) 62 (7,7) 57 (7,8) 5 (6,1) Lives in the following condition, n (%) Geriatric Home 16 (2,0) 16 (2,2) 0 (0,0) With Small Children 106 (13,1) 97 (13,3) 9 (11,0) Overcrowded 36 (4,4) 31 (4,3) 5 (6,1) Habits, n (%) Alcoholic 1 (0,1) 1 (0,1) 0 (0,0) Smoker 117 (14,4) 105 (14,4) 12 (14,6) PAS 1 (0,1) 1 (0,1) 0 (0,0) Hematic Compromise, n (%) Anemia 10 (1,2) 9 (1,2) 1 (1,2) Immune System Compromise, n (%) Immunologic Compromise + 139 (17,2) 132 (18,1) 7 (8,5) Neurologic Compromise, n (%) Stroke 8 (1,0) 8 (1,1) 0 (0,0) Dementia 4 (0,5) 4 (0,5) 0 (0,0) Other Neurologic Disease 33 (4,1) 32 (4,4) 1 (1,2) Hepatic Compromise, n (%) Chronic Hepatic Disease ** 11 (1,4) 9 (1,2) 2 (2,4) Pulmonary Compromise , n (%) Pulmonary Disease 69 (8,5) 59 (8,1) 10 (12,2) Renal Compromise, n (%) Chronic Kidney Disease 141 (17,4) 125 (17,2) 16 (19,5) Renal Replacement Therapy 137 (16,9) 122 (16,8) 15 (18,3) Cardiovascular Compromise, n (%) Hypertension 423 (52,2) 381 (52,3) 42 (51,2) Cardiac Disease * 252 (31,1) 219 (30,1) 33 (40,2) Other, n (%) Catheter probe 26 (3,2) 26 (3,6) 0 (0,0) Tracheostomy 1 (0,1) 1 (0,1) 0 (0,0) Abbreviations : qPCR (quantitative polymerase chain reaction), S.D. (Standard deviation), P.A.S. (psychoactive substances), C.O.P.D. (Chronic obstructive pulmonary diseases), O.H.S.A.S. (obstructive hypopnea sleep apnea syndrome). * Includes heart failure, coronary disease, myocardial infarction , and arrhythmia. + Includes recent transplants, cancer, rheumatoid arthritis, lupus, other autoimmune disease, H.I.V., AIDS, chemotherapy, biological therapy, and leukopenia by any cause. ** Includes chronic hepatic diseases such as viral or autoimmune hepatitis and cirrhosis. Table 2 . Vaccination rates in accordance with local guidelines. Total population n = 810 60 years or older n = 258 Pulmonary disease n= 69 Cardiac disease* n= 252 Immunologic compromise n= 258 Cirrhotic n= 2 Diabetic n= 125 Smoker n= 117 Alcoholic n= 1 Asplenia n= 0 Pneumococcal vaccine ratio n (%) 87/258 (33) 9/69 (13) 43/252 (17) 36/258 (13,9) 0/2 (0) 18/125 (14,4) 12/117 (10,2) 0/1 (0) 0/0 (0) Total population n= 810 60 years or older n = 258 Pulmonary disease n= 69 Cardiac disease* n= 252 Immunologic compromise + n= 139 CHD ++ n= 11 Diabetic n= 125 RRT n= 137 Morbid obesity Δ n= 0 Influenza vaccine ratio n (%) 11/258 (38,7) 25/69 (36,2) 95/252 (37,6) 40/108 (37) 4/11 (36,3) 45/125 (36) 56/137 (40,8) 0/0 (0) Abbreviations : CHD (Chronic hepatic disease), RRT (Renal replacement therapy) * Includes heart failure, coronary disease, myocardial infarction , and arrhythmia. + Includes recent transplants, cancer, rheumatoid arthritis, lupus, other autoimmune disease, H.I.V., AIDS , chemotherapy, biological therapy and leukopenia by any cause. ++ Includes chronic hepatic diseases such as viral or autoimmune hepatitis and cirrhosis. Δ Cutoff point of 40 kg/m 2 body mass index was used to identify these patients. Additional Declarations No competing interests reported. Supplementary Files SupplementSpn1.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4294799","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":294743900,"identity":"7825a1fd-b85c-450a-bbdd-8659e98da8c1","order_by":0,"name":"Juan Olivella-Gomez","email":"","orcid":"","institution":"Universidad de La Sabana","correspondingAuthor":false,"prefix":"","firstName":"Juan","middleName":"","lastName":"Olivella-Gomez","suffix":""},{"id":294743901,"identity":"08a09bb3-1e22-455d-8785-a3e9beffb346","order_by":1,"name":"Julián Lozada","email":"","orcid":"","institution":"Universidad de La Sabana","correspondingAuthor":false,"prefix":"","firstName":"Julián","middleName":"","lastName":"Lozada","suffix":""},{"id":294743902,"identity":"d569d17e-492c-4473-820e-45608055adfb","order_by":2,"name":"Lina Méndez-Castillo","email":"","orcid":"","institution":"Clínica Universidad de La Sabana","correspondingAuthor":false,"prefix":"","firstName":"Lina","middleName":"","lastName":"Méndez-Castillo","suffix":""},{"id":294743903,"identity":"8515edae-e8a4-4abb-881a-556711fe22d4","order_by":3,"name":"André Emilio Viñán Garcés","email":"","orcid":"","institution":"Clínica Universidad de La Sabana","correspondingAuthor":false,"prefix":"","firstName":"André","middleName":"Emilio Viñán","lastName":"Garcés","suffix":""},{"id":294743904,"identity":"6a67a774-18fa-4a3d-9ed6-4184e5b3c31b","order_by":4,"name":"Cristian C. 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According to the Global Burden of Disease (GBD), LRTI etiology is most frequently attributed to microorganisms such as \u003cem\u003eStreptococcus pneumoniae\u003c/em\u003e,\u003cem\u003e Haemophilus influenzae\u003c/em\u003e type b (Hib), influenza viruses, and respiratory syncytial virus (RSV), among others [2]. \u003cem\u003eS. pneumoniae\u003c/em\u003e stands out as the principal contributor to morbidity and mortality resulting from infectious diseases across the globe [3]. Notably, the highest burden of pneumococcal disease (PD) has been documented in the most vulnerable populations, namely, at the extremes of age and those with chronic comorbid conditions [4]. Several risk factors have been associated with PD in adults, including advanced age, chronic medical comorbidities, and immunocompromising conditions [5, 6]. In contrast, others have been postulated in children, such as nasopharyngeal pneumococcal colonization (NPC) [7].\u003c/p\u003e\n\u003cp\u003eNasopharyngeal carriage is considered the first step toward invasive pneumococcal disease (IPD) in children [7]. This colonization is possible due to several mechanisms, including the evasion of mucus entrapment by capsular polysaccharide, biofilm formation, expression of adhesion proteins, inhibition of complement proteins, and release of bacteriocins to mediate competition with local microbiota [8]. The systemic repercussions of NPC have been explored in the pediatric population [9], and a relationship with the development of acute respiratory infections has been established, especially when a high pneumococcal carriage density was present [10]. In adults, several risk factors for colonization have been described, such as smoking, living with children, and residence in a nursing home [11]; however, the relationship with LRTI is still unclear in adults.\u003c/p\u003e\n\u003cp\u003eThis study aims to determine the prevalence of \u003cem\u003eSpn \u003c/em\u003eNPC and to evaluate the relationship between NPC and the development of LRTIs or other important clinical outcomes (i.e., number of hospitalizations or mortality due to infectious diseases) in adult patients with comorbidities. Furthermore, it explores factors associated with NPC colonization, assesses the adherence of patients to anti-\u003cem\u003eSpn\u003c/em\u003e vaccination based on current local guidelines, and thus identifying specific patient subgroups that may derive substantial benefits from inclusion in vaccination programs. \u003c/p\u003e\n"},{"header":"Materials And Methods","content":"\u003cp\u003eThis prospective multicenter cohort study in adult patients with chronic diseases from four outpatient clinics in Bogot\u0026aacute; \u0026ndash; Colombia. The protocol and informed consent were developed by the Translational Science in Infectious Diseases and Critical Care Medicine (TSID-CCM) research group from the Universidad de La Sabana. These were reviewed and authorized by the Institutional Review Board/Independent Ethics Committee (IRB/EC) of the participating institutions. Ethical supervision ensured informed consent was obtained from all study participants or their authorized representatives.\u003c/p\u003e\n\u003cp\u003eInclusion criteria included individuals aged 18 years and older with at least one chronic disease that were actively attending one of the four participating centers between December 2020 and March 2022. Definitions of comorbidities are detailed in \u003cstrong\u003esupplementary material 1.\u003c/strong\u003e The exclusion criteria included patients with evidence of respiratory symptoms (e.g., rhinorrhea, fever, or expectoration) or diagnosis of community-acquired pneumonia (CAP) during the prior to 90 days according to the criteria of the American Thoracic Association (ATS) - Infectious Diseases Society of America (IDSA) [12]. Also, subjects admitted to the hospital during the previous 7 days of enrollment or limited to providing biological-type samples were also excluded from the study.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cu\u003eDefinitions \u003c/u\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNPC was defined as the identification of \u003cem\u003eSpn\u003c/em\u003e by either conventional culture method further confirmed through matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) or sigmoidal curve amplification of both pneumolysin (ply) and autolysin (lytA) genes by quantitative polymerase chain reaction (qPCR) in nasopharyngeal aspirates (NPA). Furthermore, CAP diagnosis was determined using the definition of IDSA/ATS guidelines during the follow-up [12]. The vaccination scheme was evaluated based on the specific conditions of the patient and the indications based on the local guidelines for anti-\u003cem\u003eSpn \u003c/em\u003evaccination [13]. \u003c/p\u003e\n\u003cp\u003eFinally, the composite variable termed \u0026ldquo;unfavorable outcome\u0026rdquo; was constructed of patients who developed CAP, were hospitalized due to an infectious cause, whether by \u003cem\u003eSpn\u003c/em\u003e or other microorganisms or that succumbed to pneumonia or another infectious cause at any point during the follow-up period.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cu\u003eData Collection\u003c/u\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eData collection was carried out by a dedicated research assistant, who gathered sociodemographic details of medical history, including comorbidities, living conditions, and lifestyle habits. Participants were also required to provide a verifiable vaccination record or based on medical records. The data collection process used an Electronic Case Report Form (eCRF) developed within the Research Electronic Data Capture (REDCap) platform (version 8.11.11 provided by Vanderbilt University, Nashville, Tenn.), hosted by Universidad de Sabana. Follow-up data was collected by phone calls at 6, 12, and 18 months after the date of enrollment. \u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cu\u003eSample Collection\u003c/u\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eFor all patients enrolled in the study after signing informed consent, trained nursing staff collected NPA samples with an 8 mm nelaton probe (Medex, INVIMA 2008DM - 0001689 R2, Colombia) and 8-10 cc rinsing infusion of physiological saline solution (PSS) of sodium chloride 0. 9% (Baxter, Viaflex) at 10 - 15 cm in the posterior nostril of each participant according to the guidelines of the WHO (World Health Organization) Pneumococcal Carriage Working Group in 2013 [14].\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cu\u003eLaboratory procedures\u003c/u\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eIn the laboratory, 100 𝜇L of nasopharyngeal aspirate (NPA) was immediately inoculated on blood agar and incubated at 37\u0026deg;C +/- 2\u0026deg;C for 24-48 hours in 5% CO2. Alpha-hemolytic colonies were selected, underwent optochin sensitivity testing, and sensitive strains were identified using (MALDI-TOF) mass spectrometry. \u0026quot;Suspected cases\u0026quot; were defined as colonization with \u003cem\u003eSpn\u003c/em\u003e when alpha-hemolytic colonies showed optochin sensitivity \u0026gt; 14 mm [15]. \u0026quot;Confirmed cases\u0026quot; had MALDI-TOF scores \u0026gt; 1.8 [16]. Additionally, a qPCR approach targeting ply and lytA genes was employed, adhering to specific criteria for pneumococcal colonization identification, including Ct \u0026lt; 35 (17-19] and characteristic melt curve profiles (\u003cstrong\u003eFigure 2\u003c/strong\u003e) [20]. Information regarding conventional culture, primer selection, run cycle, and standard curve identification for ply and lytA gene identification and specific criteria for colonization identification can be found in the online supplement. (\u003cstrong\u003eSupplementary material 3\u003c/strong\u003e)\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cu\u003eFollow-up period \u003c/u\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThroughout the follow-up period, phone interviews were systematically conducted with each patient at 6, 12, and 18 months from the enrollment date unless their demise or dissent of participation was previously known. These interviews aimed to gather information on instances of hospitalization, including the cause and duration, and to inquire about the development of pneumonia. If pneumonia occurred, patients were asked to provide their medical records. Then, a detailed chart review assessed the identified etiology and details of antibiotic use, including the duration of therapy and clinical outcomes. In cases where the patient had passed away, details such as the date and cause of death were meticulously recorded. Vaccination status was updated if the patient had been vaccinated during the study period. The inquiry spanned the last 6 months preceding the call.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cu\u003eStatistical analysis \u003c/u\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eA descriptive analysis was developed with measures of central tendency (mean or median) and dispersion, standard deviation (SD), and interquartile range (IQR) depending on normality distribution, respectively identified by the Shapiro-Wilk test for quantitative variables and frequencies with percentages for qualitative variables. Pneumococcal NPC period prevalence was calculated as a proportion of confirmed cases over the total number of subjects included in the study over the period of recruitment. Demographic variables and comorbidities were compared between the colonized and non-colonized groups to determine heterogeneity by applying the chi-square and Fisher\u0026apos;s exact tests for categorical variables; on the other hand, Student\u0026apos;s T-test or the Mann-Whitney U test was employed to assess continuous variables, depending on their distribution. \u003c/p\u003e\n\u003cp\u003eA multivariate logistic regression model was carried out to identify factors associated with colonization, adjusting for age to incorporate demographic details upon admission. The stepwise logistic regression method incorporated variables with a significance level at or below 0.20 in the preceding univariate analysis. Additionally, to investigate the impact of colonization on adverse outcomes, a composite variable named unfavorable outcomes, as described above, was considered across the 18-month follow-up period. This subsequent model was adjusted for age, vaccination status, and renal replacement therapy; this adjustment addressed potential selection bias given considerable recruitment from patients undergoing renal replacement therapy. Odds ratios (OR) and a 95% confidence interval (95% CI) were computed using the exponential values derived from the coefficients of the final model. All statistical analyses were performed using IBM SPSS Statistics for Mac, version 22.0, Armonk, NY: I.B.M. Corp.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eBetween December 2020 and March 2022, 810 patients were enrolled, with 82 (10.1%) identified as colonized through conventional culture and/or the qPCR method. In the overall cohort, the average age of the study population was 62 years, with a standard deviation of \u0026plusmn; 15 years, and females represented 48.6% (394/810) of the cohort. The predominant comorbidity among the studied population was hypertension (52% [423/810]), followed by cardiac conditions (31% [252/810]) and chronic kidney disease (CKD) (17.4% [141/810]); all the other comorbid conditions are presented in \u003cstrong\u003eTable 1\u003c/strong\u003e. Regarding environmental factors, 13.1% (106/810) of the patients lived with small children, and 14.4% (117/810) were smokers. Other detailed demographic and clinical characteristics for the overall cohort and stratified by \u003cem\u003eSpn\u003c/em\u003e colonization are provided in \u003cstrong\u003e(Supplementary Material 2)\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003eRegarding vaccination, 31.6% (256/810) of patients had received the influenza vaccine during the prior year, while 10.7% (87/810) had been administered a version of the anti\u003cem\u003e-Spn\u0026nbsp;\u003c/em\u003evaccine before study enrollment. Among those who received the pneumococcal vaccine, 50% (44/87) were administered the PPSV-23, 11.4% (10/87) received PCV-13, and 3.4% (3/87) were given the PSSV+PCV scheme. Notably, 33.3% (29/87) of individuals could not specify the type of pneumococcal vaccine they received but were aware of having received it. Only 1.1% (1/87) reported receiving PCV-10. Further details regarding vaccination within each subgroup based on local guidelines can be found in (\u003cstrong\u003eTable 2\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003eOver the 18-month follow-up period, 3.5% (29/810) of the cohort developed pneumonia, comprising 12 cases at 6 months, 13 at 12 months, and 4 cases at 18 months. In total, 20.2% (164/810) of participants were hospitalized for any cause during the follow-up, resulting in 248 admissions: 76 at 6 months, 89 at 12 months, and 83 at 18 months. Among these hospitalizations, 46 were attributed to infectious causes at 6 months, 56 at 12 months, and 40 at 18 months, contributing to 142 hospitalizations included in the composite outcome variable of unfavorable outcome. The mortality rate was 4.1% (34/810) at 6 months, 1.7% (13/776) during the following 6 months, and reached 1.4% (11/763) during the last 6 months for a total of 7.2% (58/810) during the entire 18-month follow-up period. Additional insights into the observed outcomes at each time point are visually presented in (\u003cstrong\u003eFigure 1\u003c/strong\u003e), providing a comprehensive overview of the cohort\u0026apos;s trajectory over the specified period.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eOutcomes\u0026nbsp;\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe \u003cem\u003eSpn\u003c/em\u003e NPC period prevalence was determined to be 10.1% (82/810) during the patient observation period. Over the 18-month follow-up, 28.3% (230/810) of patients developed any of the three considered outcomes within the unfavorable outcome variable. A multivariate logistic regression was conducted to explore the correlation between comorbidities and \u003cem\u003eSpn\u003c/em\u003e colonization. In this analysis, chronic kidney disease was identified as a risk factor for colonization, showing an odds ratio (OR, [95% CI]) of 2.48 (1.01 \u0026ndash; 6.15), \u003cem\u003ep\u0026nbsp;\u003c/em\u003e= 0.04. Similarly, cardiac diseases presented a statistically significant risk factor, albeit crossing the confidence interval, with an OR of 1.62 (0.99 - 2.66), \u003cem\u003ep\u003c/em\u003e = 0.05. Although significant in the univariate analysis, chronic hepatic disease did not demonstrate a correlation in this multivariate analysis. Details on specific outcomes for the univariate and multivariate analysis can be found in (\u003cstrong\u003eFigure 3)\u003c/strong\u003e. Hosmer-Lemeshow test for binary logistic regression models demonstrated the goodness-of-fit test (p=0.703).\u003c/p\u003e\n\u003cp\u003eSimilarly, a multivariate binary logistic regression analysis was conducted to examine whether colonization by \u003cem\u003eS. pneumoniae\u003c/em\u003e predisposed patients to develop an unfavorable outcome, as previously defined. This analysis, adjusted for age, vaccination status, and the need for renal replacement therapy, revealed that colonization by either traditional culture or qPCR showed no statistically significant correlation with unfavorable outcomes (OR [95% CI]) (1.17 [0.69 - 1.98], \u003cem\u003ep\u003c/em\u003e = 0.54). \u0026nbsp;Further information regarding both univariate and multivariate analyses can be found in the online supplement (\u003cstrong\u003eSupplementary material 4-5\u003c/strong\u003e). Moreover, a sub-analysis specifically for LTRI development showed that colonization was not a risk factor for LTRI development taking into account the bias that the low number of events represent (OR [95% CI]) (0.64 [0.14 - 2.78], \u003cem\u003ep\u003c/em\u003e = 0.55) (\u003cstrong\u003eSupplementary material 6\u003c/strong\u003e). Age was demonstrated to be independently associated with unfavorable outcomes in the multivariate analysis (1.81 [1.28 - 2.58], \u003cem\u003ep\u0026nbsp;\u003c/em\u003e\u0026lt; 0.01). As expected, the need for renal replacement therapy emerged as a significant contributor to unfavorable outcomes in the multivariate analysis (5.10 [3.43 - 7.58], \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.01). Specific outcomes from the multivariate analysis are detailed in (\u003cstrong\u003eFigure 3B)\u003c/strong\u003e, and the Hosmer-Lemeshow test for binary logistic regression models demonstrated the goodness-of-fit test (\u003cem\u003ep\u003c/em\u003e=0.548).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis prospective study performed a comprehensive clinical and microbiological assessment of patients with comorbid conditions to determine the prevalence of nasopharyngeal colonization and its impact on clinical outcomes during an 18-month period. We identified a low rate of pneumococcal colonization among Colombian, a low-middle income country, comorbid adults. Moreover, we found that \u003cem\u003eSpn\u003c/em\u003e frequently colonized patients with CKD and cardiac diseasesand that these comorbid conditions were independently associated with nasopharyngeal colonization by \u003cem\u003eSpn\u003c/em\u003e. Finally, we found no correlation between \u003cem\u003eSpn\u003c/em\u003e colonization and the development of either LRTIs, a higher number of hospitalizations, or higher mortality rates due to related infectious causes. \u003c/p\u003e\n\u003cp\u003eThe reported \u003cem\u003eSpn\u003c/em\u003e colonization of 10.1% [82/810) aligns with findings from prior studies in adults, which have reported a prevalence range of 1-10% [15, 16]. In a recent meta-analysis performed by our group, we found an overall prevalence of 6%, and a subgroup analysis prevalence of 2% for adults only [21]. However, the majority of these studies were performed in high-income countries, in healthy volunteers, or in specific groups of comorbidities [e.g., HIV patients). For instance, Carvalho \u003cem\u003eet al. \u003c/em\u003eperformed a study in Kenya in healthy participants, reporting a rate of 6.4% [n=450) in adults \u0026gt;18 years , and Palmu \u003cem\u003eet al. \u003c/em\u003ereported a 5,23% prevalence in healthy adults \u0026gt;65 years [m=592) [23]. Conversely, comorbidity-focused studies, such as those published by Heinsbroek \u003cem\u003eet al.\u003c/em\u003e and Dayie \u003cem\u003eet al.\u003c/em\u003e in Malawi and Ghana, show higher rates [21.3%, 10.0%) in adults with HIV and sickle cell anemia, respectively [24, 25]. Studies by Milucky \u003cem\u003eet al. \u003c/em\u003eand Roca-Oporto \u003cem\u003eet al.\u003c/em\u003e undertaken in developed nations like the US and Spain report lower rates (1.8% to 5,6%) in individuals with solid organ transplants and chronic diseases [26, 27]. Notably, patients with influenza-related respiratory symptoms exhibit rates as high as 31% [28]. Therefore, our findings are novel because they assessed the nasopharyngeal colonization by \u003cem\u003eSpn \u003c/em\u003ein a broader cohort of patients with multiple chronic comorbid conditions in a lower-income country, using traditional cultures and rtPCR-based techniques, making these results more generalizable. \u003c/p\u003e\n\u003cp\u003eInterestingly, this real-world study found a low anti-\u003cem\u003eSpn \u003c/em\u003evaccination rate among adults with comorbid conditions. Also, we found a low colonization rate despite suboptimal vaccination rates per local guidelines. In contrast, prior literature has shown that before the introduction of the conjugate vaccine in state schedules, Nicoletti \u003cem\u003eet al\u003c/em\u003e. and Blossom \u003cem\u003eet al.\u003c/em\u003e identified in Brazil and Uganda high proportions of culture-based colonization in adult HIV patients, 16% and 18%, respectively [29, 30], and in the U.S., Becker-Dreps \u003cem\u003eet al.\u003c/em\u003e found in older adults with general comorbidity a 1.9% colonization rate [31]. Following the incorporation of conjugate vaccines (PCV 7, 10, 13, 15, and 20), Drayss \u003cem\u003eet al. \u003c/em\u003efound in adults \u0026gt; 65 years from geriatric homes in Germany with low comorbidity levels, colonization rates of 0% [32]. Notably, our results highlight the need for more robust vaccination campaigns in adults with chronic comorbid conditions in countries with limited resources, as it is evident that solid vaccination campaigns could reduce IPD in adults [33]. \u003c/p\u003e\n\u003cp\u003eVan Hoek and Pekuz \u003cem\u003eet al.\u003c/em\u003e studies have indicated a relationship between CKD and IPD [34, 35]. Also, some studies have highlighted better outcomes and survival rates in vaccinated patients with comorbid conditions [36, 37]. However, limited research explores CKD\u0026apos;s link to colonization. Cardiovascular disease (CVD) and heart failure are frequently associated with pneumococcal disease [38-40], but their association with colonization risk remains uncertain across studies [41]. Thus, our finding that CKD and chronic cardiac diseases are independently associated with nasopharyngeal \u003cem\u003eSpn-\u003c/em\u003ecolonization highlights the importance of vaccination in these groups of patients. \u003c/p\u003e\n\u003cp\u003eFinally, we did not find an association between \u003cem\u003eSpn \u003c/em\u003ecolonization and the development of any of the three unfavorable outcomes, which contradicts the currently available data on children. This finding is novel as, to our knowledge, this study is the first study exploring this relationship in adults with comorbid conditions. One possible explanation for our findings and how they differ from what has been previously reported in children is that adults have, as a result of prior exposure events to \u003cem\u003eSpn\u003c/em\u003e, generated an adaptive immune response to \u003cem\u003eSpn\u003c/em\u003e proteins, which would confer broad protection from disease caused by all serotypes of \u003cem\u003eSpn\u003c/em\u003e. Alternatively, during childhood, these individuals were colonized by versions of \u003cem\u003eSpn\u003c/em\u003e that carry capsule types most frequently associated with disease, and now, due to the production of antibodies to these capsule types, they are more likely to be colonized by strains not as capable of causing severe infection. Therefore, further studies are needed to understand the etiology of LRTI and unfordable outcomes in patients with comorbid conditions. \u003c/p\u003e\n\u003cp\u003eOur study has some limitations that should be mentioned. First, our cohort size is relatively small, potentially impacting the ability to draw statistically significant associations. However, the study was powered to identify statistical differences, and more importantly, to the best of our knowledge, this is the first study assessing nasopharyngeal colonization in adults with comorbidities, rendering our findings applicable to a significant demographic subset. Second, we found a low prevalence of pneumococcal colonization that could be attributed to the inherent difficulty in culturing \u003cem\u003eSpn\u003c/em\u003e. Nevertheless, the study employed molecular tests to augment the likelihood of successful isolations, enhancing the precision of our analysis. Furthermore, our study overlapped with the COVID-19 pandemic, which may have impacted social dynamics, underestimating the real behavior of the colonization phenomena [42]. \u003c/p\u003e\n\u003cp\u003eIn conclusion, this novel study reinforces existing evidence that comorbidities such as CKD and cardiac diseases increase susceptibility to pneumococcal colonization. These findings underscore the imperative need for vaccination in this population. Vaccination rates, particularly for pneumococcal vaccines, were suboptimal, highlighting the urge to implement adherence to vaccination guidelines. Finally, we found that nasopharyngeal colonization by \u003cem\u003eSpn\u003c/em\u003e was not associated with unfavorable outcomes in this population, including the development of LRTI. There is a need for further research to understand the complex interactions between colonization, comorbidities, and clinical outcomes.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eStatements \u0026amp; Declarations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e: This project was funded by M.S.D. Colombia, a subsidiary of Merck \u0026amp; Co., Inc., RAHWAY, NJ, USA and Universidad de La Sabana grant number (MED-285-2020) L.F.R.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePotential Conflict of Interest:\u0026nbsp;\u003c/strong\u003eAll authors have no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisclosure Statement:\u003c/strong\u003e The authors report there are no competing interests to declare.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e: Conceptualization: J.L., J.O.G., L.F.R.; Data curation: J.L., J.O.G., L.M.C., A.E.V.G., V.E., E.D.I.P., C.C.S.M., I.G.B., L.D.V., A.M.C., L.F.R.; Formal analysis: J.L., J.O.G., L.M.C., Y.V.F., A.A.G., V.E., E.D.I.P., C.C.S.M., L.F.R.; Funding acquisition: L.F.R.; Investigation: J.L., L.M.C., Y.V.F., A.E.V.G., V.E., A.A.G., E.D.I.P., D.F.J., L.D.V., G.P.R.C., J.A.R.O., L.F.R.; Methodology: J.L., J.O.G., Y.V.F., A.A.G., V.E., D.F.J., J.P.S., D.F.J., L.F.R.; Project administration: J.L., E.D.I.P., C.C.S.M., A.M.C., L.F.R.; Software: J.L., C.C.S.M., L.F.R.; Supervision: A.A.G., A.M.C., L.F.R.; Validation: J.L., Y.V.F., A.E.V.G., VE, E.D.I.P., C.C.S.M., I.G.B., G.P.R.C., J.A.R.O., L.F.R.; Visualization: J.L., J.O.G., L.M.C., A.E.V.G., VE, E.D.I.P., C.C.S.M., A.M.C., L.F.R.; Roles/Writing \u0026ndash; original draft: J.L., J.O.G., L.M.C., E.D.I.P., C.C.S.M., A.E.V.G., VE, A.A.G., L.F.R.; and Writing \u0026ndash; review \u0026amp; editing: J.L., J.O.G., L.M.C., E.D.I.P., C.C.S.M., I.G.B., A.E.V.G., VE, A.A.G., L.F.R. All authors have approved the submitted version and agreed to be personally accountable for the author\u0026apos;s contributions and to ensure that questions related to the accuracy or integrity of any part of the work. This article has an online supplement.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement\u003c/strong\u003e: Available by request to the corresponding authors.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eOrganization WH. . The Top 10 Causes of Death Globally: Who [Internet]. 2020 [Available from: https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death.\u003c/li\u003e\n\u003cli\u003eAnderson R, Feldman C. The Global Burden of Community-Acquired Pneumonia in Adults, Encompassing Invasive Pneumococcal Disease and the Prevalence of Its Associated Cardiovascular Events, with a Focus on Pneumolysin and Macrolide Antibiotics in Pathogenesis and Therapy. Int J Mol Sci. 2023;24(13). https://doi.org/10.3390/ijms241311038\u003c/li\u003e\n\u003cli\u003eCedrone F, Montagna V, Del Duca L, Camplone L, Mazzocca R, Carfagnini F, et al. The Burden of Streptococcus pneumoniae-Related Admissions and In-Hospital Mortality: A Retrospective Observational Study between the Years 2015 and 2022 from a Southern Italian Province. Vaccines (Basel). 2023;11(8). https://doi.org/10.3390/vaccines11081324\u003c/li\u003e\n\u003cli\u003eSeveriche-Bueno DF, Severiche-Bueno DF, Bastidas A, Caceres EL, Silva E, Lozada J, et al. Burden of invasive pneumococcal disease (IPD) over a 10-year period in Bogota, Colombia. Int J Infect Dis. 2021;105:32-9. https://doi.org/10.1016/j.ijid.2021.02.031\u003c/li\u003e\n\u003cli\u003eFukuda H, Onizuka H, Nishimura N, Kiyohara K. Risk factors for pneumococcal disease in persons with chronic medical conditions: Results from the LIFE Study. 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Incidence of pneumococcal disease from 2003 to 2019 in children \u0026le;17 years in England. Pneumonia. 2023;15(1). https://doi.org/10.1186/s41479-022-00103-3\u003c/li\u003e\n\u003cli\u003eClaassen-Weitz S, Lim KYL, Mullally C, Zar HJ, Nicol MP. The association between bacteria colonizing the upper respiratory tract and lower respiratory tract infection in young children: a systematic review and meta-analysis. Clin Microbiol Infec. 2021;27(9):1262-70. https://doi.org/10.1016/j.cmi.2021.05.034\u003c/li\u003e\n\u003cli\u003eAlmeida ST, Paulo AC, Froes F, de Lencastre H, S\u0026aacute;-Leao R. Dynamics of Pneumococcal Carriage in Adults: A New Look at an Old Paradigm. J Infect Dis. 2021;223(9):1590-600. https://doi.org/10.1093/infdis/jiaa558\u003c/li\u003e\n\u003cli\u003eMetlay JP, Waterer GW, Long AC, Anzueto A, Brozek J, Crothers K, et al. 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Vaccine. 2013;32(1):165-79. https://doi.org/10.1016/j.vaccine.2013.08.062\u003c/li\u003e\n\u003cli\u003eBurckhardt I, Panitz J, Burckhardt F, Zimmermann S. Identification of Streptococcus pneumoniae: Development of a Standardized Protocol for Optochin Susceptibility Testing Using Total Lab Automation. Biomed Res Int. 2017;2017:4174168. https://doi.org/10.1155/2017/4174168\u003c/li\u003e\n\u003cli\u003eDubois D, Segonds C, Prere MF, Marty N, Oswald E. Identification of clinical Streptococcus pneumoniae isolates among other alpha and nonhemolytic streptococci by use of the Vitek MS matrix-assisted laser desorption ionization-time of flight mass spectrometry system. J Clin Microbiol. 2013;51(6):1861-7. https://doi.org/10.1128/JCM.03069-12\u003c/li\u003e\n\u003cli\u003eCarvalho Mda G, Tondella ML, McCaustland K, Weidlich L, McGee L, Mayer LW, et al. Evaluation and improvement of real-time PCR assays targeting lytA, ply, and psaA genes for detection of pneumococcal DNA. J Clin Microbiol. 2007;45(8):2460-6. https://doi.org/10.1128/JCM.02498-06\u003c/li\u003e\n\u003cli\u003eGladstone RA, Lo SW, Lees JA, Croucher NJ, van Tonder AJ, Corander J, et al. International genomic definition of pneumococcal lineages, to contextualise disease, antibiotic resistance and vaccine impact. EBioMedicine. 2019;43:338-46. https://doi.org/10.1016/j.ebiom.2019.04.021\u003c/li\u003e\n\u003cli\u003eEpping L, van Tonder AJ, Gladstone RA, The Global Pneumococcal Sequencing C, Bentley SD, Page AJ, et al. SeroBA: rapid high-throughput serotyping of Streptococcus pneumoniae from whole genome sequence data. Microb Genom. 2018;4(7). https://doi.org/10.1099/mgen.0.000186\u003c/li\u003e\n\u003cli\u003eValdarchi C, Dorrucci M, Mancini F, Farchi F, Pimentel de Araujo F, Corongiu M, et al. Pneumococcal carriage among adults aged 50 years and older with co-morbidities attending medical practices in Rome, Italy. Vaccine. 2019;37(35):5096-103. https://doi.org/10.1016/j.vaccine.2019.06.052\u003c/li\u003e\n\u003cli\u003eLozada J, Gomez JO, Serrano-Mayorga CC, Vinan Garces AE, Enciso V, Mendez-Castillo L, et al. Streptococcus pneumoniae as a colonizing agent of the Nasopharynx - Oropharynx in adults: A systematic review and meta-analysis. Vaccine. 2024. https://doi.org/10.1016/j.vaccine.2024.03.041\u003c/li\u003e\n\u003cli\u003eAbdullahi O, Nyiro J, Lewa P, Slack M, Scott JA. The descriptive epidemiology of Streptococcus pneumoniae and Haemophilus influenzae nasopharyngeal carriage in children and adults in Kilifi district, Kenya. Pediatr Infect Dis J. 2008;27(1):59-64. https://doi.org/10.1097/INF.0b013e31814da70c\u003c/li\u003e\n\u003cli\u003ePalmu AA, Kaijalainen T, Saukkoriipi A, Leinonen M, Kilpi TM. Nasopharyngeal carriage of Streptococcus pneumoniae and pneumococcal urine antigen test in healthy elderly subjects. Scand J Infect Dis. 2012;44(6):433-8. https://doi.org/10.3109/00365548.2011.652162\u003c/li\u003e\n\u003cli\u003eHeinsbroek E, Tafatatha T, Phiri A, Ngwira B, Crampin AC, Read JM, et al. Persisting high prevalence of pneumococcal carriage among HIV-infected adults receiving antiretroviral therapy in Malawi: a cohort study. Aids. 2015;29(14):1837-44. https://doi.org/10.1097/Qad.0000000000000755\u003c/li\u003e\n\u003cli\u003eDayie N, Tetteh-Ocloo G, Labi AK, Olayemi E, Slotved HC, Lartey M, et al. Pneumococcal carriage among sickle cell disease patients in Accra, Ghana: Risk factors, serotypes and antibiotic resistance. PLoS One. 2018;13(11):e0206728. https://doi.org/10.1371/journal.pone.0206728\u003c/li\u003e\n\u003cli\u003eMilucky J, Carvalho MG, Rouphael N, Bennett NM, Talbot HK, Harrison LH, et al. Streptococcus pneumoniae colonization after introduction of 13-valent pneumococcal conjugate vaccine for US adults 65 years of age and older, 2015-2016. Vaccine. 2019;37(8):1094-100. https://doi.org/10.1016/j.vaccine.2018.12.075\u003c/li\u003e\n\u003cli\u003eRoca-Oporto C, Cebrero-Cangueiro T, Gil-Marques ML, Labrador-Herrera G, Smani Y, Gonzalez-Roncero FM, et al. Prevalence and clinical impact of Streptococcus pneumoniae nasopharyngeal carriage in solid organ transplant recipients. BMC Infect Dis. 2019;19(1):697. https://doi.org/10.1186/s12879-019-4321-8\u003c/li\u003e\n\u003cli\u003eKrone CL, Wyllie AL, van Beek J, Rots NY, Oja AE, Chu ML, et al. Carriage of Streptococcus pneumoniae in aged adults with influenza-like-illness. PLoS One. 2015;10(3):e0119875. https://doi.org/10.1371/journal.pone.0119875\u003c/li\u003e\n\u003cli\u003eNicoletti C, Brandileone MCC, Guerra MLS, Levin AS. Prevalence, serotypes, and risk factors for pneumococcal carriage among HIV-infected adults. Diagn Micr Infec Dis. 2007;57(3):259-65. https://doi.org/10.1016/j.diagmicrobio.2006.08.021\u003c/li\u003e\n\u003cli\u003eBlossom DB, Namayanja-Kaye G, Nankya-Mutyoba J, Mukasa JB, Bakka H, Rwambuya S, et al. Oropharyngeal colonization by among HIV-infected adults in Uganda:: assessing prevalence and antimicrobial susceptibility. International Journal of Infectious Diseases. 2006;10(6):458-64. https://doi.org/10.1016/j.ijid.2006.05.010\u003c/li\u003e\n\u003c/ol\u003e\n\u003col start=\"31\"\u003e\n\u003cli\u003eBecker-Dreps S, Kistler CE, Ward K, Killeya-Jones LA, Better OM, Weber DJ, et al. Pneumococcal Carriage and Vaccine Coverage in Retirement Community Residents. J Am Geriatr Soc. 2015;63(10):2094-8. https://doi.org/10.1111/jgs.13651\u003c/li\u003e\n\u003cli\u003eDrayss M, Claus H, Hubert K, Thiel K, Berger A, Sing A, et al. Asymptomatic carriage of Neisseria meningitidis, Haemophilus influenzae, Streptococcus pneumoniae, Group A Streptococcus and Staphylococcus aureus among adults aged 65 years and older. PLoS One. 2019;14(2):e0212052. https://doi.org/10.1371/journal.pone.0212052\u003c/li\u003e\n\u003cli\u003eBonten MJ, Huijts SM, Bolkenbaas M, Webber C, Patterson S, Gault S, et al. Polysaccharide conjugate vaccine against pneumococcal pneumonia in adults. N Engl J Med. 2015;372(12):1114-25. https://doi.org/10.1056/NEJMoa1408544\u003c/li\u003e\n\u003cli\u003evan Hoek AJ, Andrews N, Waight PA, Stowe J, Gates P, George R, et al. The effect of underlying clinical conditions on the risk of developing invasive pneumococcal disease in England. J Infect. 2012;65(1):17-24. https://doi.org/10.1016/j.jinf.2012.02.017\u003c/li\u003e\n\u003cli\u003ePekuz S, Soysal A, Akkoc G, Atici S, Yakut N, Gelmez GA, et al. Prevalence of Nasopharyngeal Carriage, Serotype Distribution, and Antimicrobial Resistance of Streptococcus pneumoniae among Children with Chronic Diseases. Jpn J Infect Dis. 2019;72(1):7-13. https://doi.org/10.7883/yoken.JJID.2017.410\u003c/li\u003e\n\u003cli\u003eBond TC, Spaulding AC, Krisher J, McClellan W. Mortality of Dialysis Patients According to Influenza and Pneumococcal Vaccination Status. Am J Kidney Dis. 2012;60(6):959-65. https://doi.org/10.1053/j.ajkd.2012.04.018\u003c/li\u003e\n\u003cli\u003eGilbertson DT, Guo HF, Arneson TJ, Collins AJ. The association of pneumococcal vaccination with hospitalization and mortality in hemodialysis patients. Nephrol Dial Transpl. 2011;26(9):2934-9. https://doi.org/10.1093/ndt/gfq853\u003c/li\u003e\n\u003cli\u003eFeldman C, Anderson R. Recent advances in our understanding of Streptococcus pneumoniae infection. F1000Prime Rep. 2014;6:82. https://doi.org/10.12703/P6-82\u003c/li\u003e\n\u003cli\u003eCorrales-Medina VF, Musher DM, Shachkina S, Chirinos JA. Acute pneumonia and the cardiovascular system. Lancet. 2013;381(9865):496-505. https://doi.org/10.1016/S0140-6736(12)61266-5\u003c/li\u003e\n\u003cli\u003eViasus D, Garcia-Vidal C, Manresa F, Dorca J, Gudiol F, Carratala J. Risk stratification and prognosis of acute cardiac events in hospitalized adults with community-acquired pneumonia. J Infect. 2013;66(1):27-33. https://doi.org/10.1016/j.jinf.2012.09.003\u003c/li\u003e\n\u003cli\u003eBranche AR, Yang H, Java J, Holden-Wiltse J, Topham DJ, Peasley M, et al. Effect of prior vaccination on carriage rates of Streptococcus pneumoniae in older adults: A longitudinal surveillance study. Vaccine. 2018;36(29):4304-10. vhttps://doi.org/10.1016/j.vaccine.2018.05.107\u003c/li\u003e\n\u003cli\u003eFacciola A, Lagana A, Genovese G, Romeo B, Sidoti S, D'Andrea G, et al. Impact of the COVID-19 pandemic on the infectious disease epidemiology. J Prev Med Hyg. 2023;64(3):E274-E82. https://doi.org/10.15167/2421-4248/jpmh2023.64.3.2904\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003e Distribution of comorbidities in \u003cem\u003eStreptococcus pneumoniae\u003c/em\u003e (\u003cem\u003eSpn\u003c/em\u003e) colonized and no \u003cem\u003eSpn\u003c/em\u003e colonized patients.\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"680\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.284241531664215%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.642120765832107%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal patients sampled n=810\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.23858615611193%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNo \u003cem\u003eSpn\u003c/em\u003e colonized\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=728\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.835051546391753%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eSpn\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;colonized\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=82\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristic\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.284241531664215%\" valign=\"top\"\u003e\n \u003cp\u003eAge mean, S.D.\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.642120765832107%\" valign=\"top\"\u003e\n \u003cp\u003e62\u0026plusmn;15\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.23858615611193%\" valign=\"top\"\u003e\n \u003cp\u003e62\u0026plusmn;15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.835051546391753%\" valign=\"top\"\u003e\n \u003cp\u003e64\u0026plusmn;15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.284241531664215%\" valign=\"top\"\u003e\n \u003cp\u003eGender female, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.642120765832107%\" valign=\"top\"\u003e\n \u003cp\u003e394 (48,6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.23858615611193%\" valign=\"top\"\u003e\n \u003cp\u003e357 (49,0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.835051546391753%\" valign=\"top\"\u003e\n \u003cp\u003e37 (45,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.284241531664215%\" valign=\"top\"\u003e\n \u003cp\u003eHealth Care Worker, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.642120765832107%\" valign=\"top\"\u003e\n \u003cp\u003e62 (7,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.23858615611193%\" valign=\"top\"\u003e\n \u003cp\u003e57 (7,8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.835051546391753%\" valign=\"top\"\u003e\n \u003cp\u003e5 (6,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eLives in the following condition, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.284241531664215%\" valign=\"top\"\u003e\n \u003cp\u003eGeriatric Home\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.642120765832107%\" valign=\"top\"\u003e\n \u003cp\u003e16 (2,0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.23858615611193%\" valign=\"top\"\u003e\n \u003cp\u003e16 (2,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.835051546391753%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0,0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.284241531664215%\" valign=\"top\"\u003e\n \u003cp\u003eWith Small Children\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.642120765832107%\" valign=\"top\"\u003e\n \u003cp\u003e106 (13,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.23858615611193%\" valign=\"top\"\u003e\n \u003cp\u003e97 (13,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.835051546391753%\" valign=\"top\"\u003e\n \u003cp\u003e9 (11,0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.284241531664215%\" valign=\"top\"\u003e\n \u003cp\u003eOvercrowded\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.642120765832107%\" valign=\"top\"\u003e\n \u003cp\u003e36 (4,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.23858615611193%\" valign=\"top\"\u003e\n \u003cp\u003e31 (4,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.835051546391753%\" valign=\"top\"\u003e\n \u003cp\u003e5 (6,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eHabits, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.284241531664215%\" valign=\"top\"\u003e\n \u003cp\u003eAlcoholic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.642120765832107%\" valign=\"top\"\u003e\n \u003cp\u003e1 (0,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.23858615611193%\" valign=\"top\"\u003e\n \u003cp\u003e1 (0,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.835051546391753%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0,0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.284241531664215%\" valign=\"top\"\u003e\n \u003cp\u003eSmoker\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.642120765832107%\" valign=\"top\"\u003e\n \u003cp\u003e117 (14,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.23858615611193%\" valign=\"top\"\u003e\n \u003cp\u003e105 (14,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.835051546391753%\" valign=\"top\"\u003e\n \u003cp\u003e12 (14,6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.284241531664215%\" valign=\"top\"\u003e\n \u003cp\u003ePAS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.642120765832107%\" valign=\"top\"\u003e\n \u003cp\u003e1 (0,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.23858615611193%\" valign=\"top\"\u003e\n \u003cp\u003e1 (0,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.835051546391753%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0,0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eHematic Compromise, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.284241531664215%\" valign=\"top\"\u003e\n \u003cp\u003eAnemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.642120765832107%\" valign=\"top\"\u003e\n \u003cp\u003e10 (1,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.23858615611193%\" valign=\"top\"\u003e\n \u003cp\u003e9 (1,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.835051546391753%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eImmune System Compromise, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.284241531664215%\" valign=\"top\"\u003e\n \u003cp\u003eImmunologic Compromise\u003csup\u003e+\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.642120765832107%\" valign=\"top\"\u003e\n \u003cp\u003e139 (17,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.23858615611193%\" valign=\"top\"\u003e\n \u003cp\u003e132 (18,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.835051546391753%\" valign=\"top\"\u003e\n \u003cp\u003e7 (8,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNeurologic Compromise, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.284241531664215%\" valign=\"top\"\u003e\n \u003cp\u003eStroke\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.642120765832107%\" valign=\"top\"\u003e\n \u003cp\u003e8 (1,0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.23858615611193%\" valign=\"top\"\u003e\n \u003cp\u003e8 (1,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.835051546391753%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0,0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.284241531664215%\" valign=\"top\"\u003e\n \u003cp\u003eDementia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.642120765832107%\" valign=\"top\"\u003e\n \u003cp\u003e4 (0,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.23858615611193%\" valign=\"top\"\u003e\n \u003cp\u003e4 (0,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.835051546391753%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0,0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.284241531664215%\" valign=\"top\"\u003e\n \u003cp\u003eOther Neurologic Disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.642120765832107%\" valign=\"top\"\u003e\n \u003cp\u003e33 (4,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.23858615611193%\" valign=\"top\"\u003e\n \u003cp\u003e32 (4,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.835051546391753%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eHepatic Compromise, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.284241531664215%\" valign=\"top\"\u003e\n \u003cp\u003eChronic Hepatic Disease\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.642120765832107%\" valign=\"top\"\u003e\n \u003cp\u003e11 (1,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.23858615611193%\" valign=\"top\"\u003e\n \u003cp\u003e9 (1,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.835051546391753%\" valign=\"top\"\u003e\n \u003cp\u003e2 (2,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ePulmonary Compromise\u003cstrong\u003e, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.284241531664215%\" valign=\"top\"\u003e\n \u003cp\u003ePulmonary Disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.642120765832107%\" valign=\"top\"\u003e\n \u003cp\u003e69 (8,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.23858615611193%\" valign=\"top\"\u003e\n \u003cp\u003e59 (8,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.835051546391753%\" valign=\"top\"\u003e\n \u003cp\u003e10 (12,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eRenal Compromise, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.284241531664215%\" valign=\"top\"\u003e\n \u003cp\u003eChronic Kidney Disease\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.642120765832107%\" valign=\"top\"\u003e\n \u003cp\u003e141 (17,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.23858615611193%\" valign=\"top\"\u003e\n \u003cp\u003e125 (17,2)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.835051546391753%\" valign=\"top\"\u003e\n \u003cp\u003e16 (19,5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.284241531664215%\" valign=\"top\"\u003e\n \u003cp\u003eRenal Replacement Therapy\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.642120765832107%\" valign=\"top\"\u003e\n \u003cp\u003e137 (16,9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.23858615611193%\" valign=\"top\"\u003e\n \u003cp\u003e122 (16,8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.835051546391753%\" valign=\"top\"\u003e\n \u003cp\u003e15 (18,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eCardiovascular Compromise, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.284241531664215%\" valign=\"top\"\u003e\n \u003cp\u003eHypertension\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.642120765832107%\" valign=\"top\"\u003e\n \u003cp\u003e423 (52,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.23858615611193%\" valign=\"top\"\u003e\n \u003cp\u003e381 (52,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.835051546391753%\" valign=\"top\"\u003e\n \u003cp\u003e42 (51,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.284241531664215%\" valign=\"top\"\u003e\n \u003cp\u003eCardiac Disease\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.642120765832107%\" valign=\"top\"\u003e\n \u003cp\u003e252 (31,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.23858615611193%\" valign=\"top\"\u003e\n \u003cp\u003e219 (30,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.835051546391753%\" valign=\"top\"\u003e\n \u003cp\u003e33 (40,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eOther, n (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.284241531664215%\" valign=\"top\"\u003e\n \u003cp\u003eCatheter probe\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.642120765832107%\" valign=\"top\"\u003e\n \u003cp\u003e26 (3,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.23858615611193%\" valign=\"top\"\u003e\n \u003cp\u003e26 (3,6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.835051546391753%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0,0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.284241531664215%\" valign=\"top\"\u003e\n \u003cp\u003eTracheostomy\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.642120765832107%\" valign=\"top\"\u003e\n \u003cp\u003e1 (0,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.23858615611193%\" valign=\"top\"\u003e\n \u003cp\u003e1 (0,1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.835051546391753%\" valign=\"top\"\u003e\n \u003cp\u003e0 (0,0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbbreviations\u003c/strong\u003e: qPCR (quantitative polymerase chain reaction), S.D. (Standard deviation), P.A.S. (psychoactive substances), C.O.P.D. (Chronic obstructive pulmonary diseases), O.H.S.A.S. (obstructive hypopnea sleep apnea syndrome).\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e*\u003c/strong\u003e Includes heart failure, coronary disease, myocardial infarction\u003cu\u003e,\u003c/u\u003e and arrhythmia.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e+ Includes recent transplants, cancer, rheumatoid arthritis, lupus, other autoimmune disease, H.I.V., AIDS,\u0026nbsp;chemotherapy, biological therapy, and leukopenia by any cause.\u003c/p\u003e\n \u003cp\u003e** Includes chronic hepatic diseases such as viral or autoimmune hepatitis and cirrhosis.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2\u003c/strong\u003e. Vaccination rates in accordance with local guidelines.\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"916\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.22707423580786%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal population\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en = 810\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.388646288209607%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e60 years or older\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en = 258\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.353711790393014%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePulmonary disease\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en= 69\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.279475982532752%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCardiac disease*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en= 252\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.336244541484715%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eImmunologic compromise\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en= 258\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.37117903930131%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCirrhotic\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en= 2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.279475982532752%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDiabetic\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en= 125\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.951965065502183%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSmoker\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en= 117\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51528384279476%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAlcoholic n= 1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAsplenia\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en= 0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.22707423580786%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePneumococcal vaccine ratio\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.388646288209607%\"\u003e\n \u003cp\u003e87/258 (33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.353711790393014%\"\u003e\n \u003cp\u003e9/69\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.279475982532752%\"\u003e\n \u003cp\u003e43/252 (17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.336244541484715%\"\u003e\n \u003cp\u003e36/258\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(13,9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.37117903930131%\"\u003e\n \u003cp\u003e0/2\u003c/p\u003e\n \u003cp\u003e(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.279475982532752%\"\u003e\n \u003cp\u003e18/125 (14,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.951965065502183%\"\u003e\n \u003cp\u003e12/117 (10,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51528384279476%\"\u003e\n \u003cp\u003e0/1\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\"\u003e\n \u003cp\u003e0/0\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.22707423580786%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal population\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en= 810\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.388646288209607%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e60 years or older\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en = 258\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.353711790393014%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePulmonary disease\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en= 69\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.279475982532752%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCardiac disease*\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en= 252\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.336244541484715%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eImmunologic compromise\u003csup\u003e+\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en= 139\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.37117903930131%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCHD\u003csup\u003e++\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en= 11\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.279475982532752%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDiabetic\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en= 125\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.951965065502183%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRRT\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en= 137\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51528384279476%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMorbid obesity\u003c/strong\u003e\u003cstrong\u003e\u003csup\u003e\u0026nbsp;\u0026Delta;\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en= 0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.22707423580786%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eInfluenza vaccine ratio\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.388646288209607%\"\u003e\n \u003cp\u003e11/258\u003c/p\u003e\n \u003cp\u003e(38,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.353711790393014%\"\u003e\n \u003cp\u003e25/69\u003c/p\u003e\n \u003cp\u003e(36,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.279475982532752%\"\u003e\n \u003cp\u003e95/252\u003c/p\u003e\n \u003cp\u003e(37,6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.336244541484715%\"\u003e\n \u003cp\u003e40/108\u003c/p\u003e\n \u003cp\u003e(37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.37117903930131%\"\u003e\n \u003cp\u003e4/11\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(36,3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.279475982532752%\"\u003e\n \u003cp\u003e45/125\u003c/p\u003e\n \u003cp\u003e(36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.951965065502183%\"\u003e\n \u003cp\u003e56/137\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(40,8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.51528384279476%\"\u003e\n \u003cp\u003e0/0\u003c/p\u003e\n \u003cp\u003e(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"917\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbbreviations\u003c/strong\u003e: CHD (Chronic hepatic disease), RRT (Renal replacement therapy)\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e*\u003c/strong\u003e Includes heart failure, coronary disease, myocardial infarction\u003cu\u003e,\u003c/u\u003e and arrhythmia.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" valign=\"top\"\u003e\n \u003cp\u003e+ Includes recent transplants, cancer, rheumatoid arthritis, lupus, other autoimmune disease, H.I.V., AIDS\u003cu\u003e,\u003c/u\u003e chemotherapy, biological therapy and leukopenia by any cause.\u003c/p\u003e\n \u003cp\u003e++ Includes chronic hepatic diseases such as viral or autoimmune hepatitis and cirrhosis.\u003c/p\u003e\n \u003cp\u003e\u0026Delta; Cutoff point of 40 kg/m\u003csup\u003e2\u0026nbsp;\u003c/sup\u003ebody mass index was used to identify these patients.\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-4294799/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4294799/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose\u003c/strong\u003e: \u003cem\u003eStreptococcus pneumoniae (Spn\u003c/em\u003e) is the primary bacterial cause of lower respiratory tract infections (LRTI) globally, particularly impacting older adults and children. While \u003cem\u003eSpn\u003c/em\u003e colonization in children is linked to LRTI, its prevalence and consequences in adults with comorbidities remains uncertain. This study aims to provide novel data in that regard.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: This is a prospective study of outpatient adults with chronic diseases. Data on demographics, vaccination, and clinical history was gathered. Nasopharyngeal aspirate samples were examined for Spn colonization using traditional cultures and PCR. Patients were followed for 18 months, with colonization prevalence calculated and factors influencing colonization and its impact on clinical outcomes analyzed through logistic regressions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: 810 patients were enrolled, with 10.1% (82/810) identified as colonized. The mean (SD) age was 62 years (±15), and 48.6% (394/810) were female. Major comorbidities included hypertension (52.2% [423/810]), cardiac conditions (31.1% [252/810]), and chronic kidney disease (17.4% [141/810]). Among all, 31.6% (256/810) received the influenza vaccine in the previous year, and 10.7% (87/810) received anti-\u003cem\u003eSpn\u003c/em\u003e vaccines. Chronic kidney disease (OR 95% CI; 2.48 [1.01-6.15], p=0.04) and chronic cardiac diseases (OR 95% CI; 1.62 [0.99-2.66], p=0.05) were independently associated with Spn colonization. However, colonization did not increase the risk of LRTI (OR 95%CI; 0.64 [0.14-2.79], p=0.55) or unfavorable outcomes (OR 95% CI;1.17 [0.14-2.79], p=0.54) during follow-up.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e: Chronic kidney and cardiac diseases are independently associated with \u003cem\u003eSpn\u003c/em\u003e colonization, underscoring the importance of vaccination in this population. \u003cem\u003eSpn \u003c/em\u003ecolonization was not associated with LRTI/unfavorable outcomes in adult patients with chronic comorbidities.\u003c/p\u003e","manuscriptTitle":"The Relation of Nasopharyngeal Colonization by Streptococcus pneumoniae in Comorbid Adults with Pneumonia and Unfavorable Outcomes in a Low-Middle Income Country","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-29 15:08:12","doi":"10.21203/rs.3.rs-4294799/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"1f9c6cc8-b43f-4a42-a57e-40594b20b637","owner":[],"postedDate":"April 29th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-05-06T12:48:45+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-29 15:08:12","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4294799","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4294799","identity":"rs-4294799","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}