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 ~  Abstract
 ~ Introduction
 ~  Materials and Me...
 ~ Results
 ~ Discussion
 ~  References
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  Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 36  |  Issue : 1  |  Page : 93-96
 

Utility of GeneXpert in the diagnosis, reliance on urine microscopy and clinical characteristics of genitourinary tuberculosis at a tertiary care hospital


Department of Medicine and Infectious Diseases, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India

Date of Web Publication2-May-2018

Correspondence Address:
Dr. Ajaz Nabi Koul
Department of Medicine and Infectious Diseases, SKIMS, Srinagar, Jammu and Kashmir
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijmm.IJMM_18_114

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 ~ Abstract 

Background: One-third of the world's population is infected with tuberculosis (TB) with new infection occurring every second. In humans, TB is primarily caused by Mycobacterium tuberculosis(MTB). Genitourinary TB (GUTB) is still a major health problem in many developing countries including India and had been declared by the World Health Organisation as 'public health emergency' in 1993. Materials and Methods: This is a prospective study conducted at a tertiary care hospital involving 46 patients who presented with clinical feature suggestive of GUTB – urine specimens of these 46 patients were analysed for acid–fast bacilli (AFB), AFB culture, GeneXpert, and other relevant investigations were done to reach the diagnosis. Majority of patients were female (65.25%). This is especially relevant to rural and low socioeconomic areas in developing countries where women's health is worse than men's (in terms of nutrition); women's risk of disease may be increased. Most of our patients were above 30 years of age and exhibited nonspecific symptoms such as dysuria, haematuria and frequency. All patients were put on antitubercular drugs and followed as per the guidelines. Conclusion: The sample size in the present study is small to arrive at a brisk inference, but it may safely be postulated that yield of detection for GeneXpert may be improved using multiple sampling, especially the early morning ones. It is also pertinent to mention here that GeneXpert may not be able to pick up mutant genomes.


Keywords: Genitourinary tuberculosis, GeneXpert, urine microscopy


How to cite this article:
Koul AN, Kassana BA, Rather AR. Utility of GeneXpert in the diagnosis, reliance on urine microscopy and clinical characteristics of genitourinary tuberculosis at a tertiary care hospital. Indian J Med Microbiol 2018;36:93-6

How to cite this URL:
Koul AN, Kassana BA, Rather AR. Utility of GeneXpert in the diagnosis, reliance on urine microscopy and clinical characteristics of genitourinary tuberculosis at a tertiary care hospital. Indian J Med Microbiol [serial online] 2018 [cited 2018 Nov 15];36:93-6. Available from: http://www.ijmm.org/text.asp?2018/36/1/93/231680



 ~ Introduction Top


Tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB) complex remains a major global public health concern and is the first leading cause of death from infectious diseases worldwide.[1],[2] In 2015, an estimated 10.4 million people developed TB and 1.8 million died from the disease.[1] Most of the estimated number of cases occurred in Asia and Africa, and smaller proportions of cases occurred in Europe and America, especially in Latin America.[1],[3],[4] Of the 6.1 million notified incident cases, extrapulmonary TB (EPTB) represents 15% of global TB burden, ranging from 8% in the Western Pacific Region to 23% in the Eastern Mediterranean Region.[1] A series of studies from industrialised countries demonstrated that the contribution of EPTB to the total TB burden has significantly increased in recent years.[5],[6] Despite the increased trend seen in several regions, EPTB is rarely given high priority in the public health sector, which is mainly because EPTB is not significantly associated with the community transmission of the disease.[5] However, considering that EPTB contributes significantly to TB-related morbidity, severe complications and disabilities, there is an urgent need to address this group of patients in international TB control strategies [5],[7],[8]

Urinary TB (UTB) is one of the most common types of EPTB and is also considered as a severe form of EPTB in clinical practice.[8],[9],[10],[11],[12],[13] About 20% of the EPTB cases reported annually are UTB.[14] The diagnosis of UTB is difficult because its symptoms are similar to other bacterial infections, which serves as the major cause for diagnosis delay and unfavourable treatment outcome of UTB patients.[10] The most important step in laboratory diagnosis of UTB is currently based on acid–fast staining and mycobacterial cultures.[10],[15]

Acid–fast staining is cheap and fast but lacks sensitivity and reproducibility.[16] Cultures on media and liquid media yield an acceptable sensitivity, whereas the time-consuming procedures and long turnaround time cannot meet the criteria of point-of-care. Recently, GeneXpert MTB/rifampin (RIF) (GeneXpert), a fully automated real-time hemi-nested PCR system, has been developed to rapid diagnosis of TB and RIF resistance in <3 h.[17],[18] The test utilises five molecular beacons that detect mutations in an 81-bp core region of the rpoB gene that are associated with RIF resistance.[19] On the basis of numerous evaluation studies, the World Health Organisation recommended this novel assay to diagnose pulmonary TB and RIF resistant in adults, as well as to diagnose EPTB and RIF resistance in adults and children.[20] Certainly, given the limited data on the utility of GeneXpert for urine samples, these recommendations do not apply to these samples.[20]

In this study, we also evaluated the performance of the GeneXpert on urine specimens for diagnosis of UTB in a country with high TB incidence.

We undertook this study to elicit the clinical profile, laboratory parameters and changing resistance patterns in genitourinary TB (GUTB) patients attending a tertiary care hospital.


 ~ Materials and Methods Top


This was a prospective study conducted at a tertiary care hospital involving 46 patients who presented with clinical feature suggestive of GUTB – urine specimens of these 46 patients were analysed for AFB, AFB culture, GeneXpert, and other relevant investigations were done to reach a diagnosis.


 ~ Results Top


A total of 46 patients of GUTB were involved in the study, of which 30 (65.25%) were female and 16 (37.78%) were male [Figure 1]. Among these, three patients (6.5%) were having associated pulmonary TB, six (13.04%) were cervical TB and two (4.34%) were abdominal TB. Urine for AFB was positive in all the 46 patients, whereas MTB culture was found positive in 13 (28%) patients only. Average haemoglobin was 12.6 g/dl and chest X-ray abnormality was present in three (6.52%) cases. In routine urine analysis, all 46 cases had pyuria, 12 (26.08%) haematuria and 3 (6.52%) casts [Figure 2]. GeneXpert was positive in 18 (39%) cases. RIF resistance was seen in two (4.34%) cases, isoniazid resistance in only one case (2.17%) and multidrug-resistant TB in one case [Figure 3].
Figure 1: Sex distribution in the study

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Figure 2: Percentage of symptoms in genitourinary tuberculosis

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Figure 3: Relative percentages of positivity of tests

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 ~ Discussion Top


The term “genitourinary tuberculosis” was coined by Hans Wildbolz(1873-1940). It represents the TB that occurs in the kidney, ureter, testis and epididymis through blood-borne infection.[21] Although GUTB was the most common subtype of EPTB in the past,[22] it was recently reported to account for <0.5% of all patients with EPTB and 1.5% of all patients with pulmonary TB.[23] Becker reported that GUTB patients associated with pulmonary TB accounted for <5% of all GUTB patients, approximately 50% of whom had a history of pulmonary TB.[24] TB of the ureter and bladder was directly transmitted from the kidney. The clinical symptoms of GUTB vary according to interactions between the host and MTB. Dysuria, hesitancy and frequency commonly occur in renal and prostatic TB and some cases of renal TB present with dysuria and flank pain.[25]

In this study, GUTB was diagnosed using the urine AFB test, urine MTB culture test and GeneXpert. Although the urine AFB test is simple, economical and rapid, it has low sensitivity and specificity for MTB. The urine MTB culture test has a higher specificity compared to the urine AFB test but requires at least 8 weeks before the results are obtained. Urine PCR can detect the presence of MTB even when the urine AFB test and the urine MTB culture test are negative, and it allows for earlier treatment by detecting MTB in its early stages. The caveat to this corollary remains that PCR for TB in urine in a high-burden country is overestimated. It may be representative for diagnosis of genitor UTB.

In this study, the majority of the patients belonged to the age group above 30. This again reflected in such studies worldwide which report a mean age of 31–58 years.[26],[27],[28],[29] This is probably due to the long latent period between the primary infection with the TB bacilli and the expression of genitourinary symptoms. The most common mode of transmission to the genitourinary tract is through haematogenous spread from pulmonary or other sites of TB. GUTB is a chronic disease and often has low-grade symptomatology with very few specific complaints. We found a wide gender inequality of GUTB in the study (65.25% females). Other such studies, especially from developing nations, have also reported gender inequalities, with females suffering more from this form of TB.[30] In this study, most of the patients presented with frequency, haematuria and dysuria, this is in agreement with many studies which have reported symptoms such as haematuria, flank pain, frequency and dysuria.[31],[32] This has been explained by many observers by the fact that even though kidney is the most frequently and primarily affected part of the urinary tract, the renal lesions are mainly asymptomatic, but vesicle lesions lead to symptoms and storage difficulties. In this study, 6.5% of patients had pulmonary TB; this is in accordance with other studies which showed that 8%–15% of patients with pulmonary TB are supposed to be at risk of developing GUTB [33]

GUTB is diagnosed by the demonstration of Mycobacterium in urine or body fluid and granulomatous lesion on histopathology. Other features which help in the diagnosis are changes in the radiographic study (intravenous pyelogram, computed tomography and chest X-ray) and raised ESR.[34],[35] Although urine AFB test is simple, economical and rapid, it has low sensitivity and specificity for MTB. The yield of direct AFB smear is low and it is positive in 30% of cases.[35] Although in this study, it was 100% probably because most of our patients were evaluated by urologists and nephrologist before seeking infectious disease consultation. In the present study, we also noticed that culture was positive in 28% of cases, this was in accordance with other studies conducted previously which that culture can be positive in 20%–97% of cases with GUTB.[35],[36]

GeneXpert studies usually have sensitivity above 90% in many studies conducted on the patient previously. However, in this study, sensitivity is only 39%. This can be explained using single sample analysis by GeneXpert as compared to 3 or 5 early morning sampling in conventional urine for AFB. As we are aware that in GUTB, AFB are intermittently shed in urine and hence the yield of single sample may be low. The early morning collection for AFB stain and that too for extended periods ranging from 3 to 5 days improves sensitivity.

The sample size in the present study is small to come to brisk inference, but it may safely be postulated that yield of detection for GeneXpert may be improved by multiple sampling, especially the early morning ones.

It is also pertinent to mention here that GeneXpert may not be able to pick up mutant genomes.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 ~ References Top

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