Extrapulmonary tuberculosis: diagnostic features

Introduction: The incidence of tuberculosis in Poland decreased from 128.5 in 100,000 in 1970 to 19.1 in 100,000 in 2010. In many countries, but not in Poland, according to the improvement of the epidemiological situation of tuberculosis (TB), the proportion of the extrapulmonary form of this disease is increasing. The aim of this study was to describe changes in extrapulmonary TB epidemiology in Poland from 1974 to 2010. Material and methods: Retrospective analysis of data from National TB Register on tuberculosis in Poland in the years 1974–2010. The percentage of extrapulmonary tuberculosis among all cases of tuberculosis, the differences in the proportion of extrapulmonary tuberculosis, and differences in various locations of lesions in this form of disease in relation to sex and age groups were assessed. Information was collected from about 626,093 cases of tuberculosis reported to the Register during the period 1972–2010. In 62,251 cases extrapulmonary tuberculosis was the only form of the disease (9.9% of all tuberculosis cases). The study material consisted of 396,344 male and 196,184 female cases; 30,885 subjects were 0–19 years of age, 191,542 were 20–39 years old, 237,256 were 40–59 years old, and 166,410 subjects were ≥ 60 years old. We compared data from the years 1974–1982 with more recent data (2002–2010). The test of proportions for two independent samples was used to assess the significance of differences in proportions. Results: The proportion of extrapulmonary tuberculosis (EPTB) among all TB cases was 11.2% in the years 1974–1982 and only 8.2% in the years 2002–2010. This difference was significant. The proportion of EPTB among all TB cases was higher in women than in men and was higher in people aged 0–19 years than in other age groups. The location of extrapulmonary tuberculosis was different in women and in men. Pleural TB was the most common form of extrapulmonary tuberculosis in both sexes with a predominance of males. Peripheral lymph nodes, bones and joints, urinary, genital, and skin TB were more common in women (these differences were significant). In the youngest age group intrathoracic lymph node TB dominated, and in the older age groups it was pleural TB. In accordance with the increase in age, the proportion of urinary tract, peripheral node, and pericardium TB increased. Central nervous system TB showed no predilection for a particular age group. Conclusions: The proportion of EPTB to all cases of TB is lower in Poland than in other countries. In addition, the proportion of EPTB had significantly decreased from 1974–1982 to 2002–2010. It may be due to difficulties in diagnosis of those forms of TB in Poland. Alternatively it is possible that those cases diagnosed in non-respiratory centres are not reported to the National TB Register.

Extrapulmonary tuberculosis (EPTB) is an important component of tuberculosis (TB) taken as a whole, but it is often underestimated. Before we can make a reliable estimation of the epidemiology of EPTB, and particularly urogenital tuberculosis (UGTB), unification of the terminology is necessary. The term “Urogenital tuberculosis” is obviously preferable to “Genitourinary tuberculosis”. Some authors understand the term “Extrapulmonary tuberculosis” as specific TB lesions of all organs, excluding bronchus, lungs, pleura and intrathoracic broncho-pulmonal lymph nodes. Others consider pleural TB as one form of EPTB – which is a reason why different authors conclude very different proportions in the spectrum of EPTB. Enigmatic tendencies were revealed also in the distribution of patients–in neighbouring regions the incidence rate may differ significantly. Many forms of EPTB are underdiagnosed: in fact, about 25 % of patients with pulmonary (PTB) and 77 % of those who died from all localizations of TB, had prostate TB – mostly having been overlooked for a lifetime. Absence of unique terms and classifications make it difficult to formulate an accurate picture of EPTB.

Antananarivo, the capital city of Madagascar, has an endemic focus of tuberculosis (TB). We specifically studied patients with extrapulmonary TB (EPTB) and grouped patients according to infected body site. The strains were characterized by IS6110 fingerprinting and compared with those isolated from patients with pulmonary TB (PTB) during the same period in order to determine the possible association between the genotype and the clinical expression of TB. A total of 316 TB patients were included in this study: 151 individuals with EPTB, 10 with both PTB and EPTB, and 155 with PTB alone. Pleural TB was the major EPTB localization (77%) and was found more often in older patients, while PTB or EPTB in which the localization was other than pleural (other EPTB) was found in younger patients. The male-to-female ratio was slightly higher in pleural TB patients (3.06:1) than in patients with other EPTB (1.35:1). There was no significant difference in the BCG status among patients with PTB, pleural TB, and other EPTB. Analysis of IS6110 patterns showed that 167 patients (52.8%) were assigned to 37 clusters of 2 to 34 patients. Analysis of the IS6110 clusters and the IS6110 families did not show any association with a particular clinical expression of the disease. Patients with PTB or other EPTB were more likely to have strains with one IS6110 copy than patients with pleural TB. The clustering rate was found to be significantly higher in female patients (62%) than in male patients (48%) (P = 0.029), suggesting that Malagasy women were more likely to progress to disease after infection than men.

Before discussing the epidemiology of extrapulmonary tuberculosis (EPTB) and particularly urogenital tuberculosis (UGTB), unification of the terminology is necessary. The term 'urogenital tuberculosis' is preferable to 'genitourinary tuberculosis', as renal and urinary tract tuberculosis is more common than genital tuberculosis. Some understand the term 'extrapulmonary tuberculosis' as a specific tuberculosis (TB) lesion of all organs excluding the bronchus, lungs, pleura and intrathoracic bronchopulmonary lymph nodes, but others consider pleural TB as one form of EPTB - and it is a reason for very different proportions in the spectrum of EPTB. Enigmatic tendencies have also been revealed in patients' distribution - in neighbouring regions the incidence rate may differ significantly. Although there is no clear explanation for these tendencies, careful study of the epidemiology of EPTB in different conditions will improve early diagnosis.

Limited information exists about the current epidemiological characteristics of extrapulmonary tuberculosis. However, pleural tuberculosis is usually considered to be a manifestation of primary tuberculosis. Our objective was to use molecular epidemiological techniques to describe the occurrence of pleural and other extrapulmonary tuberculosis in Maryland, a state with moderate tuberculosis incidence. We surveyed tuberculosis cases reported with a single site of disease in Maryland from 1996 through 2001. Genotyping of Mycobacterium tuberculosis isolates was performed with an IS6110-based restriction fragment-length polymorphism analysis. DNA clustering of strains with >5 IS6110 bands, with supporting epidemiologic information on patients, served as a proxy for recent transmission. A total of 1811 patients with tuberculosis were reported (incidence, 5.9 cases per 100,000 population). Of 1411 patients (77.9%) with cultures positive for M. tuberculosis, 1246 (88.3%) had a single site of disease, with 934 (75.0%) of these isolates having >5 IS6110 bands. Of the 934 patients included in the analyses, 729 (78.0%) had pulmonary tuberculosis, and 205 (22.0%) had extrapulmonary tuberculosis; of the latter group, 46 patients had pleural disease, and 159 patients had nonrespiratory disease. In multivariate analyses, patients with pleural tuberculosis were not significantly associated with clustered strains, compared with patients with nonrespiratory or pulmonary tuberculosis disease. Having a DNA-clustered strain was negatively associated with nonrespiratory tuberculosis, compared with pulmonary disease (adjusted odds ratio, 0.48; P = .003). Nonrespiratory extrapulmonary tuberculosis is less likely than pulmonary tuberculosis to be a result of recent infection. Pleural tuberculosis is not an appropriate indicator for recent transmission among our population.

Background:Pediatric tuberculosis (TB) is an indicator of the recent transmission of TB in the community. However, the diagnosis of pediatric TB poses a challenge to clinicians.Aims:We aimed to evaluate and compare the clinical and laboratory profile of pulmonary TB (PTB) and extra PTB (EPTB) in children and adolescents.Methods:In this retrospective observational study, children attending the pediatric TB clinic of All India Institute of Medical Sciences, Rishikesh, from August 2015 to July 2017 were included in the study. The medical case records of patients were reviewed for demography, clinical findings, investigations, and diagnosis. The clinical and laboratory characteristics of patients with PTB and EPTB were compared.Results:A total of 58 children included. Out of which, 33 (56.9%) had PTB, and 25 (43.1%) had EPTB. The EPTB cases included 15 (60%) pleural TB, 9 (36%) lymph node TB, and 1 (4%) TB meningitis patient. Fever, cough, and weight loss were the most common symptoms. Hilar lymphadenopathy was the most common radiological abnormality. Microbiological confirmation was possible in 54.5% of patients with PTB. Cough (aOR 70.326; 95% CI: 5.370–921.032) and microbiological confirmation (aOR 46.011; 95% CI: 2.073–1021.201) were more in PTB as compared to EPTB.Conclusions:PTB and EPTB are common in children and adolescents. The typical clinical manifestations and positive microbiological confirmation are less common in EPTB than PTB.Relevance for patients:TB is one of the common communicable diseases in the developing world. Diagnosis of TB in children is often challenging. Our study results help in better understanding childhood TB and EPTB clinical features and have potential to increase diagnostic yield.

Tuberculosis in Tanzania—A national survey of newly notified cases

Objective — to determine the frequency of small residual changes (SRC) and large residual changes (LRC), as well as the super large residual changes (SLRC) recommended by us after treatment of pulmo-nary tuberculosis (TB) and extrapulmonary localization organs with multi and extended resistance in HIV-positive patients, depending on the speed of diagnosis of TB and timely adequate antimycobacterial therapy (AMBT) with antiretroviral therapy (ART).Materials and methods. The clinical study involved 44 adult HIV-positive patients with multidrug-resistant TB (MDRTB) of lungs and extrapulmonary localization and those with localized TB with extensively drug-resistance (XDR TB), who were examined and treated (AMBT with ART) in accordance with national methods and standards. After treatment of TB, patients are distributed according to eight indicators into two identical groups of 22 people, depending on the simultaneous use of molecular genetic and cultural methods (group I) compared to using only cultural methods (group II).Results and discussion. The frequency of SRC and LRC in patients of group I was established in 9.0 and 23.0 % of cases, respectively, in patients of group II — in 23.0 and 41.0 %, the difference between the groups was not significant (p > 0.05). The frequency of malfunctions in patients of group I was detected in 52.0 % of cases, in patients of group II — in 36.0 % (p < 0.05). Significantly, high level of SLRC in HIV-positive patients with cured MDRTB and XDRTB with multiple injuries was obtained due to early diagnosis of TB and adequate AMBT, especially miliary TB and TB of the nervous system. A clinical case illustrates the results.Conclusions. In HIV-positive patients, after curing lung MDRTB/XDRTB in combination with organ extrapulmonary localization, it is recommended to additionally isolate SLRC, which include SRC and LRC of the lungs and extrapulmonary localization organs. Their high frequency is significantly affected by the rapid diagnosis of TB with the determination of a test for the sensitivity of Mycobacterium tuberculosis (MBT) to anti-TB drugs (PTP) and adequate AMBT against ART. Regarding SRC and LRC, they are equally common in HIV-positive patients after treatment of lung MDRTB/XDRTB or extrapulmonary localization, such as peripheral lymph nodes.

BackgroundAlthough the evidence base regarding the use of the Xpert MTB/RIF assay for diagnosis of pulmonary tuberculosis (TB) when testing respiratory samples is well established, the evidence base for its diagnostic accuracy for extrapulmonary and sputum-scarce pulmonary TB when testing non-respiratory samples is less clearly defined.MethodsA systematic literature search of 7 electronic databases (Medline, EMBASE, ISI Web of Science, BIOSIS, Global Health Database, Scopus and Cochrane Database) was conducted to identify studies of the diagnostic accuracy of the Xpert assay when testing non-respiratory samples compared with a culture-based reference standard. Data were extracted and study quality was assessed using the QUADAS-2 tool. Sensitivities and specificities were calculated on a per-sample basis, stratified by sample type and smear microscopy status and summarised using forest plots. Pooled estimates were calculated for groups with sufficient data.ResultsTwenty-seven studies with a total of 6,026 non-respiratory samples were included. Among the 23 studies comparing Xpert and culture done on the same samples, sensitivity was very heterogeneous with a median sensitivity of 0.83 (IQR, 0.68–0.94) whereas specificities were typically very high (median, 0.98; IQR, 0.89–1.00). The pooled summary estimates of sensitivity when testing smear-positive and smear-negative samples were 0.95 (95% CI 0.91–1.00) and 0.69 (95% CI 0.60-0.80), respectively. Pooled summary estimates of sensitivity varied substantially between sample types: lymph node tissue, 0.96 (95% CI, 0.72-0.99); tissue samples of all types, 0.88 (95% CI, 0.76–0.94); pleural fluid, 0.34 (95% CI, 0.24–0.44); gastric aspirates for diagnosis of sputum-scarce pulmonary TB, 0.78 (IQR, 0.68 – 0.85). Median sensitivities when testing cerebrospinal fluid and non-pleural serous fluid samples were 0.85 (IQR, 0.75-1.00) and 0.67 (IQR, 0.00-1.00), respectively.ConclusionXpert detects with high specificity the vast majority of EPTB cases with smear-positive non-respiratory samples and approximately two-thirds of those with smear-negative samples. Xpert is a useful rule-in diagnostic test for EPTB, especially when testing cerebrospinal fluid and tissue samples. In addition, it has a high sensitivity for detecting pulmonary TB when using gastric aspirate samples. These findings support recent WHO guidelines regarding the use of Xpert for TB diagnosis from non-respiratory samples.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-014-0709-7) contains supplementary material, which is available to authorized users.

BackgroundWhile tuberculosis (TB) can be diagnosed by microscopy and culture, the sensitivity of Ziehl-Neelsen staining is variable and culture results require 4 - 8 weeks to be determined. Polymerase chain reaction (PCR) and its modifications, including nested PCR, might be promising methods for the rapid diagnosis of TB.ObjectivesThis study aimed to evaluate the performance of nested PCR on urine samples of human immunodeficiency virus (HIV)-positive and -negative patients with different manifestations of clinical TB.MethodsIn a prospective study, three early-morning urine samples from 100 patients with pulmonary TB (PTB) or extrapulmonary TB (EPTB) were evaluated using a molecular target with insertion element IS6110, specific to the Mycobacterium tuberculosis genome, and nested PCR was performed. The results were analyzed with SPSS version 22.ResultsA total of 100 patients, including 74 (74%) with PTB and 26 (26%) with EPTB, were enrolled. Positive smears were seen in 38 patients (38%). Lymph nodes were the most commonly involved organ in 14 of the 26 (53.8%) EPTB patients (13.5%). Seven (23.1%) of the EPTB patients were HIV-positive. Urine PCR was positive in only 28 patients (28%). Seven HIV-positive patients with PTB showed positive urine PCR results. Moreover, PCR results were positive in only one of the seven HIV-positive subjects with EPTB. Positive PCR results were found in 20 of the 73 HIV-negative patients (27.4%) and in 8 of the 27 HIV-positive patients (29.6%). Therefore, there was no significant difference between the HIV-negative and HIV-positive patients for urine PCR (sensitivity 29.6%, specificity 72.6%; positive and negative predictive values 28% and 72%, respectively; P = 0.138).ConclusionsNested PCR showed the same sensitivity in HIV-positive and HIV-negative patients. It can be applied as a rapid technique for the diagnosis of TB.

Objective. To identify the main demographic and clinical risk factors for the development of extrapulmonary tuberculosis (EPTB).Materials and methods. A retrospective study of tuberculosis cases registered from 2016 to 2020 in the Gomel region was conducted (330 patients with EPTB and 2,505 patients with pulmonary tuberculosis). The odds ratios were calculated to assess the risk factors for the development of EPTB.Results. The prevalence of EPTB was studied over the course of five years. The most significant risk factors for the development of tuberculosis in extrapulmonary localizations have been identified.Conclusion. The risk factors for the development of EPTB are age (EPTB often develops in children and older persons), females, and in those who have had an episode of tuberculosis previously. Awareness of the predisposing factors may help physicians maintain a high index of suspicion regarding the development of EPTB.

Current Concepts in the Management of Tuberculosis

Introduction. A persistent trend towards a decrease in the incidence of extrapulmonary tuberculosis is noted both in the Omsk region and throughout the Russian FederationPurpose of the study. To study anamnestic, epidemiological and clinical features of children diagnosed with renal tuberculosis and other extrapulmonary localizations, established by typical clinical and radiological manifestations or proven bacteriologically or histologically.Materials and methods. A retrospective study data was carried out from 125 children aged 0-14 years in the period 2001-2018 with registered as «extrapulmonary tuberculosis» with or without lung involvement. Group 1 consisted of 50 patients with a typical clinical and radiological picture of tuberculosis, group 2 - 75 cases, with a specific extrapulmonary process, verified bacteriologically and/or using molecular genetic methods or histology. The differences between groups were determined using Pearson's χ2 test.Results. The predominance in the structure of confirmed and established extrapulmonary process of renal tuberculosis was established, and children living in urban areas had better accessibility of diagnostic methods for verifying extrapulmonary tuberculosis (62.7%, p < 0.05). A history of concomitant pathology (94.7%, p < 0.05) and the availability of the lesion for bacteriological or histological examination (urine, pus, punctate) increased the likelihood of diagnosis verification. Most of the considered factors for renal tuberculosis in children did not differ significantly. Hyperergic results (up to 24%, p < 0.05) of immunological tests, the presence of complaints of dysuric disorders (21%, p < 0.05) prevailing in groups of children with an established diagnosis of tuberculosis kidneys, only suggest the presence of MBT-infection and do not prove the specific nature of the disease, while systematic preventive work on the examination of the risk group allows timely diagnosis of the disease at an early stage of the disease (up to 26%, p < 0.05).Conclusion. The widespread improvement of material and technical equipment, the introduction of new diagnostic techniques (PCR of urine) into routine practice, training of medical personnel in assessing prevalence issues and early detection of the disease can improve the quality of verification of this nosology.

Underestimation of the True Specificity of the Urine Lipoarabinomannan Point-of-Care Diagnostic Assay for HIV-Associated Tuberculosis.

BackgroundThe proportion of extrapulmonary tuberculosis (EPTB) among all the reported tuberculosis (TB) cases has increased in different populations. Despite the large burden of TB in China, the epidemiology of EPTB in China remains largely understudied and the risk factors for having EPTB diagnosis in China have not been identified.MethodsTo gain insight to EPTB epidemiology in China, we analyzed TB surveillance data collected in Tianjin, China, during 2006 to 2011. The frequency of EPTB among all TB cases and within different socio-demographic groups of the study patients aged 15 years and older was determined for EPTB in general and by specific types. The distribution of socio-demographic characteristics was compared between pulmonary TB (PTB) group and EPTB group by chi-square test. Crude and multiple logistic regression-derived adjusted odds ratios (aOR) and 95% confidence intervals (CI) were determined to assess the associations between having EPTB diagnosis and each individual explanatory variable in question.ResultsAbout one-tenth (1,512/14,561) of the patients investigated in this study had EPTB. Of these 1,512 EPTB cases, about two thirds were pleural TB. Significant difference in age, occupation, and urbanity of residence were found between PTB and EPTB groups (p<0.05). Patients with EPTB diagnosis were more likely to be 65 years or older (aOR = 1.22, 95% CI: 1.02, 1.46), to be retired (aOR = 1.37, 95% CI: 1.08, 1.75), and to live in urban areas (aOR = 1 38, 95% CI: 1.22, 1.55).ConclusionsThe findings of this study extends the knowledgebase of EPTB epidemiology in developing countries and highlight the need for improved EPTB detection in China, especially in subpopulations with high risk for EPTB or having limited access to medical facilities with adequate capacity for EPTB diagnosis.