Uncomplicated Cystitis in an Adult Male Following Influenza B Virus Infection

Background

Influenza A and B viruses are important human pathogens causing seasonal outbreaks of illness and resulting in significant morbidity and mortality. While a large amount of research has been conducted into influenza A viruses, less is known about influenza B, even though it is recognized as an important pathogen [1]. Infection with an influenza virus principally causes a self-limiting respiratory illness with mild to moderate systemic symptoms, although occasionally influenza virus has been shown to disseminate through cardiac, neurological, and muscular tissues [1]. The most commonly reported complications arising from influenza infection are subsequent secondary bacterial infections often resulting in pneumonia. These secondary infections have been more commonly reported following influenza A infection, but here we present a novel case of uncomplicated urinary tract infection (cystitis) in an adult male following influenza B infection.

Case Report

Discussion

Complications of influenza virus infection typically occur in the very young, elderly, pregnant, immunocompromised, and those with cardiovascular comorbidities, and are less commonly seen in otherwise healthy adults. Pneumonia is the most common complication of seasonal influenza A infection in adults, and is categorized either as primary viral pneumonia or secondary bacterial pneumonia, cases of which account for approximately one-quarter of influenza-associated deaths [2]. Influenza B infections are typically limited to the upper respiratory tract, but can be exacerbated by severe systemic complications that may be fatal even in previously healthy individuals. Of the various neurological complications that have been reported, febrile seizures are among the most common [3]. Cardiovascular complications most typically involve myocarditis, which can be fatal even in otherwise healthy patients [4]. Musculoskeletal pathologies (myositis) that did not result in renal impairment have also been reported [3].

A clinical review of the microbiology of bacterial co-infection associated with severe influenza A infection identified multiple Gram-positive pathogens, which most commonly included Staphylococcus aureus, Streptococcus pneumoniae, and Streptococcus pyogenes [5]. While bacterial co-infections associated with influenza B infection have been reported less frequently, the same opportunistic pathogens have been observed [6,7]. Co-infection with Gram-negative organisms, including Haemophilus influenzae and Pseudomonas species, are less common [5], while E. coli co-infections are rare. A fatal case of influenza A infection in a previously healthy adult male was associated with E. coli cultured from pulmonary abscesses, although any causal relationship was complicated by the additional identification of S. aureus and Herpes simplex virus in this patient [8]. More recently, a case series reported 6 hemodialysis patients with pandemic influenza (pdmH1N1) complicated by nosocomial E. coli pneumonia [9].

Hematuria describes the presence of red blood cells in the urine, which may originate from proximal urinary tract structures such as the kidneys to more distal genitourinary tissues, requiring clinicians to consider both renal and genitourinary pathologies. There are multiple reports of influenza B infection resulting in acute renal failure as a consequence of myositis and rhabdomyolysis, occurring in both males and females, and in both pediatric [10,11] and adult patients [12]. Acute renal injury associated with influenza B virus most likely occurs as a result of myoglobinemia, marked elevation of serum creatine kinase, and acute tubular necrosis. While ultimately resulting in end-organ renal pathology, these reports highlight an initiating infection and/or inflammation of skeletal muscle, rather than direct injury to the renal or genitourinary systems. Nevertheless, direct infection of renal tissue has been documented in a case report of renal transplant from a donor positive for influenza B [13]. Biopsy of the kidney at transplantation was positive for influenza B virus by reverse transcription polymerase chain reaction (RT-PCR), although this did not result in systemic transmission of infection to the organ recipient, and there was no detectable virus on repeat biopsy at day 14 post-transplant.

Tabbutt et al. [11] describe a case of influenza B associated myocarditis and myositis requiring extracorporeal membrane oxygenation and hemodialysis in a 4-year-old girl. The patient initially presented with lethargy and dehydration, and was started on antibiotics for urinary bacteriuria (E. coli <25,000 cfu on urine culture) prior to deterioration and diagnosis of influenza B virus by nasopharyngeal swab. It is not fully clear if the presence of E. coli in the urine culture was responsible for the child’s clinical condition, or if bacteriuria occurred as a result of influenza B infection, as these matters were not the focus of the report. Nonetheless, to the best of our knowledge, this is the only other case of influenza B infection describing a possible association with urinary tract infection.

In general, bacterial infections of the renal system are less common in males compared with females, and tend to occur in pediatric and geriatric cohorts, in the immunocompromised, in patients with spinal cord injury, and following procedures involving instrumentation of the bladder or renal tract surgery [14,15]. As such, the annual incidence of uncomplicated cystitis in a healthy adult male is given as 5 infections per 10,000 men, compared with 0.5 infections per person/year in women [16,17]. Indeed, as a result of the low incidence of urinary tract infections in adult males, patients are sometimes investigated with renal tract ultrasound for the detection of structural abnormalities, but this is rarely performed for female patients with uncomplicated cystitis.

This case report represents an unusual complication following influenza B infection. A healthy adult male, with no prior history of urinary tract infection, and no structural abnormality of the renal tract, developed dysuria, frequency, and hematuria 9 days after resolution of most respiratory symptoms. This time period is consistent with cases of secondary bacterial pneumonia associated with influenza A infection, where the subsequent bacterial infection can occur up to 11 days following the initial viral illnesses [5]. The mechanism that underpins the development of uncomplicated cystitis, or indeed of any systemic complication, following influenza B infection remains unclear. Possibilities include direct infection of genitourinary epithelium by influenza B virus and weakening of local innate defences, elaboration of a hypercytokinemia state resulting in immunopathology, and/or dissemination of infected leucocytes from the site of respiratory infection to distant tissues. It is known that initial infection of respiratory epithelium with influenza A virus increases bacterial colonization, growth, and adherence to respiratory mucosa [2,18,19]. In this case, it is possible that infection with influenza B virus weakened the innate defences of the genitourinary mucosa, facilitating the urinary tract infection with E. coli.

Conclusions

We highlighted an unusual case of uncomplicated E. coli cystitis that was temporally associated with influenza B infection in an otherwise healthy adult male. This case should be considered in context alongside other bacterial complications of influenza infection, which more typically involve Gram-positive pathogens. In conclusion, primary care and emergency department clinicians should be alert to the possibility of complications associated with influenza B virus infection, including Gram-negative bacteria and conditions that affect non-respiratory systems.