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.