Prevalence of Urinary Tract Infections in Uganda: A Systematic Review and Meta-Analysis ()
1. Introduction
Infections of the urinary tract are inflammatory disorders that are caused by the abnormal growth of pathogens. Urinary tract infection (UTIs) causes’ short-term morbidity accompanied by fever, burning sensations while urinating, LAP, itching, formation of blisters and ulcers in the genital area, genital and suprapubic pain, and pyuria generally depending on the age of the person infected and the location of the urinary tract infected [1] . It may also lead to permanent damage to the kidney. Urinary tract infections (UTIs) are one of the major causes of comorbidities especially, in patients with underlying conditions, and account for major reasons for hospital visits globally [2] .
Urinary tract infections can be categorized into two namely, community-acquired or nosocomial [2] . The community-acquired urinary tract infections (CA-UTIs) are infections of the urinary system that takes place in a person’s life while in the community setting or the hospital environment within less than 48 hours of admission [2] . Community-acquired UTI is the second most common microbial infection in the community setting. The second category of UTIs is nosocomial urinary tract infections (N-UTIs) which occur after 48 hours of hospital admission, and the patient was not incubating at the time of admission or within 3 days after discharge [3] . Also, urinary tract infections may be asymptomatic, acute, chronic, and complicated or uncomplicated, and the clinical manifestations of UTIs depend on the portion of the urinary tract involved, the etiologic organisms, the severity of the infection, and the patient’s ability to mount an immune response to it. Both asymptomatic and symptomatic UTIs pose a serious threat to public health care, therefore reducing the quality of life and leading to work absenteeism [4] .
On the other hand, uncomplicated UTIs typically affect immunocompetent individuals who have no structural or neurological urinary tract abnormalities; these infections are distinguished into lower UTIs (Cystitis) and upper UTIs (pyelonephritis) [5] . Many risk factors are linked to cystitis, including female gender, a prior UTI, sexual activity, vaginal infection, diabetes, obesity, and genetic susceptibility. Furthermore, complicated UTIs are associated with factors that compromise the urinary tract or host defense, including urinary obstruction, urinary retention caused by neurological disease, immunosuppression, renal failure, renal transplantation, pregnancy, and the presence of foreign bodies such as calculi, indwelling catheters or other drainage devices [6] . Acute pyelonephritis with community onset is an ascending UTI that involved the kidneys and may be associated with bacteremia. Though pyelonephritis is less common than cystitis, it causes short-term morbidity and can lead to severe and sometimes fatal complications. The occurrence is highest among young women, followed by infants and the elderly. Likewise cystitis, the most common pathogen is E. coli followed by other Enterobacteriaceae, with a wide range of variation. Acute pyelonephritis may be treated with oral antibiotics that cover the same spectrum of pathogens as cystitis, but it calls for adequate antibiotic concentrations in the upper urinary tract and bloodstream [7] .
There are many risk factors for UTIs especially in women and these include frequent sexual intercourse, history of recurrent urinary tract infections, not urinating after intercourse, use of spermicide, and use of a diaphragm. Though the long-term adverse effects associated with uncomplicated urinary tract infections appear to be insignificant, if it is not treated, they can interfere with daily living [8] .
About 80% of uncomplicated urinary tract infections are caused by Escherichia coli, followed by Staphylococcus saprophyticus in as many as 5% to 15% of cases. Enterococci, Klebsiella species, and Proteus mirabilis account for a small percentage of overall infections. Cystitis caused by bacteria begins with the colonization of the peri-urethral skin and the anterior urethra before getting into the bladder [9] . Uropathogenic E. coli demonstrates specific virulence factors, which allow them to adhere to vaginal and uroepithelial cells, repel bactericidal activity of human serum, prevent phagocytosis by leucocytes, and production of specific cytotoxins for tissue invasion [10] . Such virulence factors and uropathogenicity are not confined to E. coli and have been shown with Proteus mirabilis and Klebsiella spp [11] . Enterobacteriaceae are the organisms most commonly responsible for both community-acquired and healthcare-associated urinary tract infections; they are found in 70% - 80% of such infections [1] . Escherichia coli (E coli) is the commonest organism causing UTIs [7] . Other causes are Klebsiella, Staphylococcus aureus, Staphylococcus saprophyticus, Proteus, Streptococcus faecalis, Streptococcus pyogenes, Candidawas also observed to produce UTI in diabetic and immunocompromised patients. A study also reported various organisms isolated as most prevalent which includes Escherichia coli, Klebsiella sp. Pseudomonas aeruginosa, Staphylococcus aureus, Proteus sp. and Serratia marcences. These organisms were isolated from urinary tract infections of patient populations [12] . The most frequent organisms isolated were Escherichia coli (E. coli), Enterococcus, Klebsiella, Enterobacter species, and Pseudomonas. Another study found Escherichia coli, Staphylococcus spp., and Pseudomonas spp. as the most prevalent bacteria. Others isolated Klebsiella spp., Proteus spp., Staphylococcus epidermidis, Staphylococcus saprophyticus, Streptococcus spp, Enterococcus spp., and Citrobacter spp. in their study [2] . This systematic review and met-analysis is to intend to ascertain the burden of UTIs prevalence in Uganda which is a public health concern due to its reoccurrence especially among the females. It is important to note that UTI not only causes acute morbidity but also is associated with renal scarring, hypertension, and chronic kidney disease in the long run, if not treated at an appropriate time with the right antimicrobial agent [12] .
2. Methods
2.1. Search Strategy
We searched two bibliographic databases, PubMed and Scopus, for studies conducted in Uganda and among Ugandans which reported investigating the prevalence, incidence, or epidemiology of urinary tract infection. We formulated our search query by combining key concepts including “urinary tract infections”, “UTI”, “bacterial isolate,” and “Uganda” with their variations using the Boolean operators (AND, OR) as presented in Table 1. We did not register a protocol for this study.
2.2. Study Selection Criteria
We included studies that met the inclusion criteria which included: (i) studies must be conducted in Uganda (ii) evidence of bacterial isolation from urine samples (iii) studies must have recruited at least 10 participants. We excluded studies that did not meet the inclusion criteria were excluded; the exclusion criteria included:(i) studies lacking evidence of primary isolation of bacteria, (ii) meta-analysis, (iii) review articles, (iv) case reports with less than 10 respondents, and (iv) studies without accessible full texts. The selection and reporting of this review followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis [13] .
2.3. Data Extraction and Critical Appraisal
Data extraction, de-duplication, and title and abstract screening were performed independently by two authors (DM and TP). For all studies that met the inclusion criteria, authors (DM and PPD) accessed the full text and screened them for eligibility for inclusion criteria. We created a standardized Microsoft Excel (2019) spreadsheet into which, we extracted and added relevant data from included studies into columns labeled as follows: author name, year of publication, Study region, sample size (number of people recruited into the study), the total number of bacteria isolated, number of respondents with UTI, period of study, sample specimen, isolation method, and study design. Critical appraisal to assess the quality and risk of bias of included studies was achieved using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for studies reporting prevalence. We assessed publication bias using funnel plots. Two authors (MD and TP) independently performed the appraisals; whenever there was a discrepancy, it was resolved by consensus.
2.4. Statistical Analysis
Using the random effect analysis model, we computed the pooled prevalence of urinary tract infectionwith 95% confidence intervals. We used the I2 statistic to assess study heterogeneity at 95%CI and interpreted as low, moderate, or high the values (≤ 25%), (25% - 75%), and (≥ 75%), respectively [14] . All meta-analyses were performed using MedCalc® Statistical Software version 22.007 (MedCalc Software Ltd, Ostend, Belgium; https://www.medcalc.org; 2023).
3. Results
A systematic search of PubMed and Scopus databases retrieved 130 studies; four (4) other studies not indexed in the databases we searched were retrieved from Google search making a total of 135 studies. Twenty-five (25) duplicates were removed, and one hundred and five (105) studies were subjected to title and abstract screening. Eighty-two (82) titles and abstracts were excluded for not meeting the inclusion criteria. The remaining twenty-three (23), which passed title and abstract screening, were further screened for all components of the inclusion criteria. At this stage, one (1) review article and fifteen (15) studies lacking relevant data were excluded. Figure 1 shows the study selection process. Critical appraisal of the eligibles studies observed discrepancies in reporting, especially in studies that used multiple specimens from individual respondents yet presented combined frequencies of various specie isolates; however, this was not considered a ground for exclusion.
Eleven (11) studies with a total of 3110 participants made the inclusion criteria (Mwaka et al., 2011; Johnson et al., 2021; Calzada et al., 2022; Nteziyaremye et al., 2020; Andabati et al., 2010; Deus et al., 2017; Odoki et al., 2020; Ocokoru et al., 2015; Gerald 2021; Abongomera et al., 2021 and Odongo et al., 2013). Two studies representing 18.2% of the eligible studies did not report the study design
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Figure 1. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) study selection framework.
they adopted, while the remaining 81.8% adopted the cross-sectional study designs. The majority of the studies, approximately 54.6% were conducted in central Uganda. Studies from the eastern region constituted 9.1% while the western and northern regions of the country have 18.2% respectively. One of the earliest works on urinary tract infections in the country was conducted in 2009 however, 54.5% of the studies were conducted within the last decade. 27.3% (n = 3) did not report the period within which they were conducted. In more than half of the studies, 63.4% (n = 7) recruited both men and women into their study while the remaining 36.4% (n = 4) was conducted among women only.
All studies collected urine samples and used conventional culture methods for microbiological isolation of uropathogens. Cumulatively, the eleven studies isolated a total of 814 uropathogens spread across fourteen (14) bacterial species. Gram-negative bacteria constitute 81.8% of the isolates while the remaining are Gram-positive. The Gram positives were predominantly; Staphylococcus species, Enterococcus, Actinomycetes, and Streptococcus species. The Gram negatives included: Pseudomonas species, Escherichia coli, Proteus species, Citrobacter, Providencia, Klebsiella species, Enterobacter, Morganella, and Acinetobacter species. The predominant uropathogens are Escherichia coli (n = 284), staphylococcus aureus (n = 122), and Klebsiella pneumoniae (n = 112). Figure 2 presents the regional distribution of the predominant uropathogens in Uganda. Selected study characteristics are presented in Table 2.
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Figure 2. Regional distribution of dominant uropathogens in Uganda.
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Table 2. Included studies with selected characteristics.
Keys: -*UTI: Urinary Tract Infections; *CRS: Cross-sectional; *TBI: Total Bacterial Isolate; *NR: Not reported; *Both: Male and Female.
Across eleven studies with a total of 3110 respondents, 775 were positive for urinary tract infections. The national pooled prevalence of urinary tract infection in Uganda is 24.92% (95% CI: ta - 26.479; I2 = 98.85 [98.56% - 99.08%]). Our meta-analysis observed that the prevalence of UTI varies across the country ranging between 3.75% - 100% (95% CI: [2.36% - 5.62%]; [96.97% - 100.00%]; I2 = 98.95% [98.7 - 99.20]). Interestingly, 69% of study respondents who tested positive for UTI were females. The distribution across other studies is presented below (Table 3, Figure 3 and Figure 4).
We performed a sub-group meta-analysis of selected study characteristics including study region, study period, and gender (Table 4). Our meta-analysis shows that although the majority of the studies were conducted in central Uganda, the northern region of the country leads in the prevalence of UTI at 35.77% (95% CI: [31.47 - 40.25]; I2: 99.0 [98.5 - 93.3]), followed by the western
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Figure 3. Forest plot of pooled prevalence of UTI in Uganda.
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Table 3. Prevalence of urinary tract infections in Uganda.
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Table 4. Sub-group meta-analytic prevalence of UTI in Uganda.
Keys: *CI: Confidence interval; I2: Measure of Heterogeneity.
region. In regards to the study period, although 27.2% of the studies did not report when the study was conducted, our meta-analysis observed an increasing trend of UTI; 2.9―fold barely a decade after the first study. However, the period between 2014-2018 accrued the highest prevalence of UTI in the country 37.46% (95%CI: [33.64 - 41.40]; I2: 95.09 [90.4 - 97.5]) (Table 4).
Several gram positive and negative uropathogens have been isolated from patients with urinary tract infections. Our systematic review and meta-analysis examined the pooled prevalence of these pathogens based on their Gram reaction. Across the different studies, Gram-negative bacteria pooled higher prevalences reflecting their dominance and role in urinary tract infection. However, two studies stood out with a higher prevalence of Gram-positive uropathogens compared to Gram-negatives; Odongo et al., 2013: 53.66% (95% CI: [42.30 - 64.75] I2: 93.3% [89.9 - 95.4]) and Calzada et al., 2022: 76.4% (95% CI: [66.22 - 85.76] I2: 93.3% [89.9 - 95.4]). Table 5 presents this information alongside forest plots in Figure 5 and Figure 6.
4. Discussion
In this meta-analysis, we systematically examined the prevalence of urinary tract infection (UTI) in Uganda by synthesizing the findings of several relevant studies (Table 2). The primary objective of our analysis was to provide a comprehensive overview of the current burden of UTIs in Uganda. By conducting a thorough search and employing rigorous inclusion criteria, we aimed to minimize bias and ensure the reliability of our findings (Figure 1). This finding underscores the significance of UTIs as a public health concern within the country. However, the distribution of UTIs was significantly higher (69%) among females compared to males (9.4%) signifying a 7.3-fold higher risk of UTIs in females (Table 2). This finding aligns with previous researches highlighting the gender disparity in UTI prevalence, where females are consistently reported to be at a higher risk [15] [16] [17] . This can partly be attributed to female biology, such as the anatomical proximity of the urethra to the anus and shorter urethral length in females, which make them more susceptible to UTIs [18] [19] . Additionally, hormonal fluctuations during menstrual cycles and pregnancy can further increase the risk among women [12] [20] . The observed gender disparity in UTI prevalence calls for targeted interventions and preventive strategies specifically tailored for females.
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Table 5. Distribution of gram-positive and negative uropathogens in Uganda.
Keys: *CI: Confidence interval; *−ve: negative; *+ve : positive; *I2: Measure of Heterogeneity.
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Figure 5. Showing forest plot for the meta-analytic prevalence of gram-negative uropathogens.
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Figure 6. Forest plot for the meta-analytic prevalence of gram-positive uropathogens in Uganda.
Also, our systematic review and meta-analysis of the regional distribution of UTI in the country show higher prevalences leaning to the northern and western regions (Figure 7) and (Table 4). These findings highlight regional differences in UTI prevalence within Uganda and emphasize the need for targeted interventions in these areas. Several factors may contribute to the higher prevalence observed in the northern and western regions. Socioeconomic disparities [21] , limited access to healthcare services [22] , lifestyle behaviors [23] , and inadequate sanitation infrastructure [24] may play a significant role in the increased burden of UTIs in these regions. To contextualize our results, we compared our findings with a recent systematic review of the etiology and prevalence of UTI in Sub-saharan Africa [25] . Notably, our estimated prevalence rate aligns with the range of prevalence reported across the sub-continent, highlighting the broader regional impact of UTIs in this part of the world. On the etiology of UTI in Uganda, our findings also align with Mwang’onde & Mchami (2022) with Escherichia coli being the prominent pathogen. Our meta-analysis, however, may be limited in some way. Firstly, lack of protocol registration. This work was
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Figure 7. Map of Uganda showing the prevalence of UTI across four regions.
conceived as a student project and the authors deem it not necessary to register as it is not requisite for studies in this category. However, the authors acknowledged that no such work exists to the best of our knowledge at the time of conducting this review. Secondly, the studies included in our analysis exhibited high levels of heterogeneity (I2) (Table 3), which may introduce variability in the prevalence estimates. Despite the limitations our analysis revealed a considerable overall prevalence of UTIs in Uganda, with a pooled prevalence of 24.92% (Table 5). Thirdly, publication bias may have influenced our results, as studies reporting lower prevalence rates may be less likely to be published. Overall, our findings provide a comprehensive overview of the prevalence of UTIs in Uganda, highlighting the significant burden of this condition within the country.
5. Conclusion
This review and meta-analysis observed a higher pooled prevalence of UTIs in Uganda however, most of the studies were done more in Central, Western and Northern region of the country with very few studies done in the Eastern region. “The most prevalent UTIs causing bacteria in Uganda as reported by the majority of researchers are Escherichia coli followed by Staphylococcus aureus, however, Calzada et al., in their study reported gram positive bacteria as the most prevalent” (Table 5). We observed in this systematic review and meta-analysis that females are more affected with UTIs in all studies than males.
6. Recommendations
More studies on UTIs are required especially, in the eastern region of the country to give a general overview of the burden of UTIs prevalence in Uganda. Further studies should recruit more males to ascertain the prevalence of UTIs among males as many studies had focused on and recruited more females than males.
Acknowledgement
We acknowledge Kampala International University Uganda (KIU) for creating a conducive environment through the provision of functional internet which enables us to accomplish this study. We thanke the Directorate of Research and Innovation KIU for their encouragement and support towards research activities in the University especially, for both staff and students.