In this paper, we presented the first thorough and comprehensive analysis of the burden UTIs from the GBD 2019 study between 1990 and 2019 at the global, regional and national levels. We estimated that more than 404.6 million (359.4-446.5) incident cases of UTIs occurred worldwide, and nearly 236 786 people (198 433 − 259 034) died of UTIs in 2019. Consistent with a previous report, UTIs are one of the most common health problems and entail a high consumption of health system resources.[17]
From 1990 to 2019, the total numbers of incident cases, deaths, and DALYs of UTIs increased markedly worldwide. The striking increase in numbers was primarily driven by population growth worldwide, specifically in low-income and middle-income countries.[15] For example, in India, the number of incident cases more than doubled between 1990 and 2019, the largest increase worldwide. Such infections therefore represent a great health care burden and, as such, demand further research to advance treatment options and improve patient care. We also showed the age-standardised incidence, death, and DALY rates all increase from 1990 to 2019. One potential explanation for this global increase in age-standardised incidence is global ageing. The risk of UTIs increases with age. Indeed, after 65 years of age in noninstitutionalized people, the rate of UTIs was 10.9% for men and 14% for women.[18] In a cross-sectional, population-based study in Sweden and Finland, among women after the age of 85, one-third were diagnosed with UTI within a 1-year period and two-thirds in a 5-year period.[19] Moreover, lengthening life spans correlate with increased time in hospitals or long-term care facilities and exposure to drug-resistant pathogens. With the ageing of the global population, UTIs in the elderly pose a unique clinical challenge in terms of healthcare burden.
Patients with type 2 diabetes mellitus are at increased risk of infections, with the urinary tract being the most frequent infection site.[20, 21] Alterations in the immune system, in addition to poor metabolic control of diabetes, and incomplete bladder emptying due to autonomic neuropathy, may all contribute to the pathogenesis of UTIs in diabetic patients.[20, 22]. An observational study of all patients with type 2 diabetes based on the UK General Practice Research Database (GPRD) found that the incidence rate of UTIs was 46.9 per 1 000 person-years among diabetic patients and 29.9 per 1 000 person-years among patients without diabetes.[23] Similarly, another American database study found that UTI diagnosis was more common in subjects with diabetes than in those without diabetes (9.4% vs 5.7%) among 89 790 matched pairs of patients with and without type 2 diabetes mellitus during 12-month follow-up.[24] Moreover, patients with diabetes have worse outcomes of UTIs than those without diabetes. Diabetes was identified as to be an important risk factor for poor clinical response after 72 h of antibiotic treatment in patients with acute pyelonephritis.[25] A previous study also showed acute pyelonephritis in elderly people with DM is associated with risk of bacteraemia, long hospitalization, and mortality.[26] According to the GBD 2017 study estimation, the incidence of diabetes increased from 11.3 million in 1990 to 22.9 million in 2017 worldwide, with a more than 100% increase.[27] The increased risk of UTIs among diabetic patients, coupled with the increase in the prevalence of diabetes mellitus worldwide may impose a substantial healthcare burden.
The increase in UTI burden might be linked to the seasonality and climate factors. An observational study in South Korea from 1997 to 1999 found that the incidence of UTIs was higher in the summer season.[28] A recent study indicated that higher temperature, more monthly sunshine hours, higher humidity, more rain days and more rainfall are associated with an increase in female acute pyelonephritis incidence in Taiwan (Province of China).[29] In our study, some countries in Tropical Latin America and Southern Latin America had high age-standardised incidence, mortality, and DALY rates over the study period, these findings are consistent with previous literature. Increased temperature enhances perspiration, causes body water loss and relative dehydration and leads to more concentrated urine and less frequent voiding.[30] Hot weather and more monthly sunshine-hours may also cause more sweating and more moisture over the perineal area which may lead to the transfer of bacteria from the rectum to the urethra in females. Moreover, the longer water residence times and increased rainfall extend the disease in wet regions due to a dilution effect causing bacteria to invade the urethra or colonize more easily, eventually causing UTIs. Seasonality and climate factors should be taken into consideration when interpreting surveillance reports and the results of interventions against UTIs.
The age-standardised incidence rates were universally higher in females than in males from 1990 to 2019. UTIs occur more frequently in women than in men, which may be due to a variety of factors, including the shorter distance between the anus (the usual source of uropathogens), the shorter length of the female urethra, the wetter environment surrounding the female urethra, and the antibacterial activity of prostate secretions.[31] However, other reasons besides anatomical differences that make women more susceptible are not clear. Previous reports indicate that the risk factors for UTIs are different in males and females, and this difference should be considered in national policy makers’ prevention programmes. Risk factors for UTIs in men may include sexual transmission by an infected female partner, anal intercourse, preputial obliteration, prostate enlargement and urological interventions, such as transrectal prostate biopsy.[32, 33] In contrast, being postmenopausal, urinary incontinence, prior history of symptomatic UTIs, and sexual activity were found to have considerable attributable burden in females.[34] Mortality rates are reported to be higher in females than in males due to the development of pyelonephritis.[35] Similar to the report, in our analyses, we observed that the age-standardised death and DALY rates were higher in females than in males from 1990 to 2019. This trend could be driven by various factors, including a higher prevalence of recurrent UTIs,[36] infection in pregnant women,[37] and infection in elder women.[38]
Our results showed that the number and rate of UTI incidence peaked in the 30–34 year age group in women in 2019. Similar results were also reported in previous studies.[11, 39] UTIs are common among young healthy women even though they generally have anatomically and physiologically normal urinary tracts. For men, the incidence of UTIs also peaked in the 30–34 year age group; however, rates increased steadily with increasing age. One potential explanation for this trend is the high prevalence of prostate enlargement in elderly men, which is an important risk factor for UTIs.[33] We also noticed that the global death and DALY rates due to UTIs increase steadily with increased age, peaking at the oldest age group for both women and men in 2019. More attention should be given to the prevention and management of UTIs in young women and older people.
A positive association was found between UTI burden and the development level of GBD regions and countries which has not been previously reported. The differences in UTI burden among SDI levels could be expected due to epidemiological characteristics of UTI-related risk factors in regions and countries with different SDI levels. According to the GBD 2017 study, high-SDI regions and countries had a higher prevalence of diabetes than low-SDI regions and countries.[27] In addition, the high-SDI regions also had a higher life expectancy than the low SDI regions.[15] Therefore, more effective interventions, such as comprehensive control of diabetes should be carried out to reverse this trend, especially in high-SDI countries.
There were several limitations of this study. First, the accuracy and robustness of GBD estimates depend to a large extent on the quality and quantity of surveillance data used in the modelling. Existing positive surveillance systems are not sensitive, and mild UTIs due to asymptomatic bacteriuria are less likely to be diagnosed and reported. Antibiotics for the treatment of UTIs seem to be a relatively easy treatment, and antibiotic self medication is highly prevalent in the developing countries due to wild availability and poor regulatory controls for selling these drugs.[40] In addition, high-quality epidemiological studies (especially on incidence and disease severity) are still rare for large portions of the world, especially in low-income regions. Thus, there might be substantial underreporting of UTIs cases in many countries. Second, the roles of specific risk factors for UTIs were not estimated, and such information could help to explain geographic and temporal patterns in the disease burden. Another limitation of our study was the inability to distinguish uncomplicated and complicated UTIs, CAUTIs and HAUTIs, which may have different outcomes.