Incidence and epidemiological features of urogenital tuberculosis among adult inhabitants in Qatar

Introduction

Tuberculosis (TB) is one of the top ten causes of death globally and is a major public health concern causing significant physical and psychosocial morbidity. In 2022, TB was the second leading cause of death from a single infectious agent worldwide, after coronavirus disease (COVID-19). TB continues to affect more than 10 million people each year, with most new TB cases occurring in the Southeast Asia region (46%), followed by the African region (23%) and the Western Pacific (18%).1, 2 About 87% of new TB cases occurred in the 30 high-burden countries, with Bangladesh, China, the Democratic Republic of Congo, India, Indonesia, Nigeria, Pakistan, and the Philippines accounting for more than two-thirds of the global total TB cases.2 Despite major efforts to increase detection, an estimated third of new TB cases are still missed each year. The unavailability of a rapid, low-cost, accurate diagnostic assay that can be used at the point of care is a major hindrance. 3

Urogenital tuberculosis (UGTB) refers to an infectious inflammation of any urogenital organ, isolated or combined, 3 representing 30 to 40% of cases of extrapulmonary tuberculosis worldwide. 3, 4 UGTB is an insidious disease in which symptoms are generally recognized late, leading to delayed diagnosis with subsequent destruction of the urogenital organ.3 Diagnosis is difficult because it does not have specific clinical features and hides under the mask of other diseases, most often urogenital tract infections, cancer, and urolithiasis.4 Few studies have been conducted on UGTB, likely due to unclear diagnostic criteria and treatment recommendations.3, 4

In Qatar, TB remains a common health problem. Although the number of TB infections in Qatar declined to 37 cases per 100,000 population in 2022, the last two years recorded a significantly higher number of TB infections than the preceding years.5 A retrospective population-based study showed extrapulmonary TB accounted for 53.6% of all TB cases in Qatar with UGTB accounting for 1.4% of cases of extrapulmonary TB.6 However, there is a lack of information about UGTB in Qatar as UGTB has not been studied in detail. The present study was undertaken to describe the incidence, demography, presentation, diagnosis, and treatment outcomes of UGTB among adult patients in Qatar.

Materials and Methods

Results

Discussion

There are few studies on UGTB, probably due to the challenges in making an accurate diagnosis arising from the diverse and nonspecific clinical presentations, a lack of clinical awareness of the possibility of TB, and the presence of other comorbidities such as HIV, diabetes, and bacterial urinary tract infections.8 Therefore, the exact incidence of UGTB is unknown. Yet, our study found that the incidence of UGTB was estimated to be 0.7 new cases per 100,000 population, accounting for 0.4% of total TB cases observed in Qatar during the study period.

In Qatar, TB is a notifiable disease. All cases of tuberculosis must be notified to the Communicable Disease Control and Prevention Section of the National Health Authority, however, there is a lack of data on UGTB. To our knowledge, our study was the first to describe UGTB in Qatar. As noted in false, our study showed that UGTB predominantly affected male patients in their 40s and from high TB prevalence countries, which is comparable to other UGTB cohort studies.9, 10, 11, 12 The illness primarily impacted expatriates who likely contracted it in their home country and experienced reactivation upon or after moving to Qatar, possibly due to stress and poor socioeconomic conditions upon arrival that improved over time. In contrast, Qatari residents likely caught the disease during childhood (through travel to countries with higher prevalence or contact with affected individuals) and experienced reactivation later in life.13

UGTB is an insidious disease where diagnosis is generally delayed due to vague clinical features and a low index of suspicion. In this study, certain patients were unexpectedly diagnosed with UGTB while undergoing diagnostic evaluations for other health issues. For instance, 11 (10.4%) individuals had been under the care of their primary care doctors for primary infertility and were later found to have UGTB following several months of diagnostic tests. Moreover, 9 (8.5%) patients were under the care of a urology team for obstructive uropathy and were ultimately diagnosed with UGTB after thorough diagnostic evaluations. The mean illness duration in our study was 86.98±129.84 days (range:17-730 days).

UGTB has no specific pathognomonic clinical features. It may appear with various clinical presentations, ranging from having no symptoms through subclinical, non-specific symptoms and signs, to obstructive uropathy and renal impairment. In our study, abdominal pain was the most common presenting symptom, which is comparable with other studies 9, 14, 15. Other presenting symptoms in this study included fever, pyuria, urinary frequency, hematuria, obstructive uropathy, and renal impairment (false). Nevertheless, all symptoms detailed in false are nonspecific and can also be present in various other illnesses such as urinary tract infections (UTIs), cancer, and urolithiasis. Therefore, a high index of suspicion is necessary for the early detection of a UGTB. Physicians must remember GUTB in all instances of UTI, urogenital cancer, and stone disease, as it can imitate these illnesses and occasionally coexist with them. Therefore, UGTB should be suspected in patients from TB-endemic areas or with a history of pulmonary tuberculosis who present with unexplained urogenital symptoms. UGTB should also be considered in cases of recurrent UTIs with sterile pyuria that do not respond to standard antibiotic therapy.

Complete blood counts, C-reactive protein (CRP), and renal function tests are nonspecific for UGTB, however, these tests are useful adjuncts to more confirmatory testing and may be useful in assessing disease response to treatment. 12 QuantiFERON-TB Gold in-tube assay with the peripheral blood is reported to have a sensitivity of 52.6% in detecting UGTB.16 In our study, QuantiFERON-TB Gold in-Tube assay was performed 95 times. It was positive in 67(70.5%) cases, while it was inconclusive in 4(4.2%) cases and negative in 24(25.3%).

The gold-standard test in diagnosing GUTB or TB, in general, involves the demonstration of the causative M. tuberculosis in clinical samples. 12 In addition, histopathological identification of caseating granuloma in urogenital biopsy tissue and the presence of acid-fast bacilli are hallmarks of UGTB.17 In most studies, the diagnosis of UGTB was made by direct identification of bacilli or culture growth and/or histopathological identification of a caseating granuloma in a urogenital specimen.8, 10, 14, 15, 18 In our study, the diagnosis of UGTB was made in 32.1% (n = 34) of patients by direct bacilli identification or culture growth and in 51.9% (n = 55) of patients by histopathology.

In 10%-33% of patients with UGTB, diagnosis is presumptive and based on a combination of strong clinical, laboratory, and radiographic evidence, without microbiological or histological confirmation plus clinical improvement after empirical antituberculosis therapy.8, 10, 18 In the current study, a presumptive diagnosis was established in 16.0%(n=17) of patients, which falls within the above-mentioned range.

The management of GUTB requires input from various specialists such as an Infectious diseases specialist, a urologist for urinary tract complications, a gynecologist for female reproductive organ issues, a radiologist for efficient image interpretation or intervention, and an infectious diseases pharmacist.

Drug treatment of UGTB should be started after microbiological or histological diagnosis and even before confirmation of the diagnosis when clinical, laboratory, and radiological data justify a preliminary diagnosis,4, 8, 19 The most acceptable treatment plan is to start a four-drug regimen, which includes isoniazid, rifampin, pyrazinamide, and ethambutol or streptomycin. In our study, all patients received anti-tuberculous therapy. The majority of patients (93.4%) were prescribed a 4-drug antituberculosis treatment, consisting of Isoniazid, Rifampicin, Ethambutol, and Pyrazinamide, whereas a small percentage (6.6%) received second-line therapy such as linezolid, moxifloxacin, amikacin, and levofloxacin. Although the optimal treatment duration has not been defined, drug-susceptible UGTB can usually be managed with regimens suitable for pulmonary tuberculosis as discussed elsewhere.19 In our study, the mean of treatment duration was 3.04±3.69(1-12 months). The variation in the duration is attributable to the fact that some patients left Qatar before treatment completion.

Almost all studies in the literature report surgical interventions in patients with UGTB, with the percentage of patients undergoing surgery varying between 8 and 95% depending on the time of diagnosis.9, 10, 18 The later the diagnosis, the greater the need for surgery due to organ damage. As a rule, surgery is done after at least 3-4 months of optimal treatment with antituberculosis medications but sometimes an emergency procedure like stenting and percutaneous nephrostomy may be needed.9 In our series, surgical intervention was reported in 73(68.9%) cases, which falls within the global range.

Conclusion

UGTB accounted for 0.4 percent of all TB cases and an incidence of 0.7 new UGTB cases per 100,000 population in Qatar. The diagnosis of UGTB is generally delayed due to vague clinical features. Awareness of UGTB is essential for physicians to suspect this disease in patients with unexplained urogenital symptoms, especially in patients from TB-endemic areas or with a history of pulmonary tuberculosis. The diagnosis of UGTB can be made by direct identification of bacilli or culture growth and/or histopathological identification of a caseating granuloma in a urogenital specimen. Drug treatment of UGTB should preferably be initiated with a 4-drug regimen after microbiological or histological diagnosis. Empirical antituberculosis therapy should be initiated when clinical, laboratory, and radiological data justify a preliminary diagnosis. Although chemotherapy is the mainstay of treatment, surgery is often required in the treatment of GUTB. We recommend conducting a prospective population-based study to overcome the limitations identified in our study.

Authors’ Contribution

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, data analysis, and interpretation, or all these areas. All authors took part in drafting, revising, or critically reviewing the article and gave final approval of the version to be published.

Source of Funding

None.

Conflict of Interest

None.