A Vaccine for Recurrent Urinary Tract Infections in Women: The Future or a Flash in the Pan?
The report in BJU International by Yang and Foley suggests that we may finally be on the right track in developing a genitourinary mucosal vaccine to prevent recurrent urinary tract infections (UTIs) in women. A urology history lesson in regard to our understanding of UTIs is needed to understand this “new” approach to the prevention of UTI; specifically, simple cystitis in women. Observant physicians in the 19th century, Robert Bentley Todd and William Osler, described the clinical course of a woman who developed cystitis before the introduction of antibiotics. If a patient with simple cystitis did not develop urosepsis or pyelonephritis and survived, the physician induced trauma of bleeding, cupping, leeches, enemas, high-dose opioids, and quinine as well as ingestion of nitric, benzoic, and even sulfuric acid, or even oil of turpentine; she would arise from bed 3 to 4 weeks later, weak and tired, but well with almost no reported possibility of developing another UTI in her lifetime.
It was Guyon, the famous French physiologist and urologist who, understanding the microbiological etiology of cystitis, proposed that women who survived the bladder infection had a reduced risk of recurrent infection due to “acquired immunity … the result of autovaccination from the absorption of toxins or bacteria in a state of modified virulence.” With the introduction of antibiotics, urologists, even Campbell in his 1956 Textbook of Urology, believed that “UTIs will soon be relegated to the waste basket of medical history,” an idea that continued into the golden age of antibiotics, the 1960s, when it was still believed that “the time has come to close the book on infectious diseases. We have basically wiped out infection in the United States” (William Stuart, Surgeon General of the United States of America, 1967). Well, that did not happen, and, in fact, with the clinical strategy of early antibiotic therapy, we may have inadvertently caused the contemporary problem of recurrent UTI in women by not allowing women with cystitis to develop their own preventive immunity. Antibiotics, even prophylatic antibiotics, cannot solve this problem and, in fact, may be contributing to future problems with development of antibiotic-resistant uropathogens and dramatic changes in our human microbial biodiversity.
So, will vaccines be the key? Certainly, the report by Yang and Foley is encouraging; however, I will go out on a limb and predict that, while we will see significant benefits with improved vaccine development, these benefits will be temporary for individuals (and perhaps even for populations) as the individual (and population-wide) microbiome adapts to the new but rather crude vaccine. It will only be further understanding of the relationship between our changing microbiome and our genome that will lead to ultimate prevention of UTIs, and that strategy might very well include a vaccine approach. In the interim, I personally will be very excited to use this vaccine in my patients and hope that the results of the ongoing international randomized placebo-controlled study will be positive.