Risk Of Extrapulmonary Tuberculosis Research Articles

Causal relationship between gut microbiota and tuberculosis: a bidirectional two-sample Mendelian randomization analysis

BackgroundGrowing evidence from observational studies and clinical trials suggests that the gut microbiota is associated with tuberculosis (TB). However, it is unclear whether any causal relationship exists between them and whether causality is bidirectional.MethodsA bidirectional two-sample Mendelian randomization (MR) analysis was performed. The genome-wide association study (GWAS) summary statistics of gut microbiota were obtained from the MiBioGen consortium, while the GWAS summary statistics of TB and its specific phenotypes [respiratory tuberculosis (RTB) and extrapulmonary tuberculosis (EPTB)] were retrieved from the UK Biobank and the FinnGen consortium. And 195 bacterial taxa from phylum to genus were analyzed. Inverse variance weighted (IVW), MR-Egger regression, maximum likelihood (ML), weighted median, and weighted mode methods were applied to the MR analysis. The robustness of causal estimation was tested using the heterogeneity test, horizontal pleiotropy test, and leave-one-out method.ResultsIn the UK Biobank database, we found that 11 bacterial taxa had potential causal effects on TB. Three bacterial taxa genus.Akkermansia, family.Verrucomicrobiacea, order.Verrucomicrobiales were validated in the FinnGen database. Based on the results in the FinnGen database, the present study found significant differences in the characteristics of gut microbial distribution between RTB and EPTB. Four bacterial taxa genus.LachnospiraceaeUCG010, genus.Parabacteroides, genus.RuminococcaceaeUCG011, and order.Bacillales were common traits in relation to both RTB and TB, among which order.Bacillales showed a protective effect. Additionally, family.Bacteroidacea and genus.Bacteroides were identified as common traits in relation to both EPTB and TB, positively associating with a higher risk of EPTB. In reverse MR analysis, no causal association was identified. No significant heterogeneity of instrumental variables (IVs) or horizontal pleiotropy was found.ConclusionOur study supports a one-way causal relationship between gut microbiota and TB, with gut microbiota having a causal effect on TB. The identification of characteristic gut microbiota provides scientific insights for the potential application of the gut microbiota as a preventive, diagnostic, and therapeutic tool for TB.

Association of Leukotriene A4 Hydrolase polymorphisms and risk of extrapulmonary tuberculosis

Genetic risk assessment of tuberculosis development and genotypic variation influence the gene and protein expression of leukotriene A4 hydrolase (LTA4H) at various sites of tuberculosis. The relationship between the genotype and phenotype of LATH4A was investigated in relation to the genetic risk assessment of extrapulmonary tuberculosis (EPTB). This study included 137 patients with EPTB and age-sex-matched 137 normal controls of the same ethnicity. LTA4H genotyping was performed using restriction fragment polymorphisms (RFLP) and protein level was analyzed using enzyme-linked immunosorbent assay (ELISA). The LTAH4 (rs.197833A/G) AG (codominant) and GG (recessive) genotypes showed 1.86 and 1.88-fold higher risks (p=0.0004 and p<0.0001 respectively) of developing EPTB. LTA4H (rs.2660898 T/G) TG (codominant) and GG (recessive) genotypes significantly increased the risk (OR:1.69, p=0.0001 and OR;1.77 p=0.008 respectively) of EPTB. Similarly, LTA4H (rs. 2540474) AG (codominant) and GG (recessive) genotypes (OR; 1.58 95% CI:1.22- 2.04, p<0.0001; OR, 1.86; 95%CI 1.37-2.52, p<0.0001) increased the risk of developing ETTB. The LTB4 protein levels were significantly higher in EPTB cases (mean ± SD; 3096.10±1287.6 pg/mL) than in controls (2304.50±644.15 pg/mL) (p<0.0001). LTA4H recessive variants influence protein levels (functional genetics), resulting in risk of EPTB.

Epidemiological and Cytokine Profile of Patients with Pulmonary and Extrapulmonary Tuberculosis in a Population of the Brazilian Amazon.

Several factors are associated with the development of different clinical forms of tuberculosis (TB). The present study evaluated epidemiological variables and cytokine levels in samples from 89 patients with TB (75 with pulmonary TB and 14 with extrapulmonary TB) and 45 controls. Cytokines were measured by flow cytometry (Human Th1/Th2/Th17 Cytometric Bead Array kit). The TB group had a higher frequency of individuals who were 39 years of age or older, married, with primary education or illiterate and had a lower family income (p < 0.05). All individuals with extrapulmonary TB reported that they were not working, and the main reasons were related to disease symptoms or treatment. The levels of IFN-γ (OR = 4.06) and IL-4 (OR = 2.62) were more likely to be elevated in the TB group (p = 0.05), and IFN-γ levels were lower in patients with extrapulmonary TB compared to those with pulmonary TB (OR = 0.11; p = 0.0050). The ROC curve was applied to investigate the diagnostic accuracy of IFN-γ levels between the different clinical forms of tuberculosis, resulting in high AUC (0.8661; p < 0.0001), sensitivity (93.85%) and specificity median (65.90%), suggesting that IFN-γ levels are useful to differentiate pulmonary TB from extrapulmonary TB. The dysregulation of pro- and anti-inflammatory cytokine levels represent a risk for the development of TB and contribute to the pathogenesis of the disease, especially variation in IFN-γ levels, which may determine protection or risk for extrapulmonary TB.

Age-specific Clinical Presentation and Risk Factors for Extrapulmonary Tuberculosis Disease in Children.

Background:Clinical presentation for extrapulmonary tuberculosis (EPTB) in children can be variable and nonspecific, leading to delayed diagnosis, disease and death. We describe the age-specific clinical presentation and identify risk factors for EPTB among children in Pakistan.Methods:In 2015–2016 in 4 facilities in Sindh, Pakistan, children were diagnosed with TB either through bacteriologic confirmation or clinical-radiologic criteria. EPTB comprised any form of TB disease that did not involve the lungs. Among children with TB disease, we report demographics, clinical characteristics and symptoms, family medical history and diagnostic test results for children with and without EPTB. We conduct age-specific regression analyses to identify factors associated with an EPTB diagnosis among children age 0–4, 5–9 and 10–14 years.Results:A total of 1163 children were diagnosed with TB disease, of which 157 (13.5%) had EPTB. Of those, 46 (29.3%) were 0–4, 53 (33.8%) were 5–9 and 58 (36.9%) were 10–14 years old. Of children with EPTB, the most frequently reported sites were lymph node (113, 72.4%) and abdominal (31, 19.9%). Weight loss was associated with an increased risk of EPTB in the 0–4-year-old (adjusted odds ratio: 2.80, 95% confidence interval: 1.05–7.47) and 10–14-year-old (adjusted odds ratio: 2.79, 95% confidence interval: 1.28–6.07) groups, and the presence of cough was associated with a decreased risk of EPTB.Conclusions:This study provides new knowledge about age-specific clinical presentation and risk factors of EPTB in children in Pakistan. Our results can help to optimize clinical algorithms designed to achieve a timely diagnosis in children with EPTB along with improved treatment outcomes.

Predictors of extrapulmonary tuberculosis among diabetic patients at Debre Markos compressive specialized hospital, Ethiopia, 2021: A retrospective cohort study

BackgroundExtrapulmonary tuberculosis is an emerging public health problem among diabetic patients. Diabetes, which causes immunosuppression, is increasingly being recognized as an independent risk factor for tuberculosis, and the two often coexist and impact each other. Therefore, this study aimed to investigate the incidence and predictors of extra pulmonary tuberculosis among diabetic patients at Debre Markos referral hospital, Northwest Ethiopia. MethodsThis institutionally-based retrospective cohort study was undertaken among 433 diabetic patients of Debre Markos compressive specialized hospital between January 2016 to December 2020. All eligible diabetic patients who full filled the inclusion criteria were included in the study. Data were entered using Epi-data Version 3.1 and analyzed using STATA Version 14. The survival time of diabetic patients was estimated using the Kaplan-Meier survival curve, and the survival time between different categorical variables was compared using the log rank test. Both bi-variable and multivariable Cox-proportional hazard regression models were fitted to identify independent predictors of tuberculosis among diabetic patients. ResultsAmong a cohort of 433 diabetic patients at Debre Markos compressive specialized hospital, 17(3.9%) developed extra pulmonary tuberculosis during the follow-up time. The total time allotted to follow up the study participants was 1101.5 person-years (PY). The overall extra pulmonary tuberculosis incidence rate was 1.5 per 100 PY with 95% CI. Using the multivariable Cox-regression analysis, age (AIR 4.8 (95% CI (1.2–20.7), 0.03), diabetic medication (AIR 1.4 (95% CI(1.24–16), 0.03), having past history of PTB before diabetic follow up initiation (AID 1.5(95% CI (3.2–6.9),0.01) and having history of alcohol (AIR (95%CI (4(1.2–13),0.02) were significantly increased the risk of extra pulmonary tuberculosis while BMI (18.5–25) AIR(95% CI (0.22 (0.06–0.76), 0.02) was associated with a rate reduction for the incidence of extra pulmonary tuberculosis. ConclusionsIn this study, we found a high rate of extra pulmonary tuberculosis among diabetic patients. Factors significantly linked with increased risk of extra pulmonary tuberculosis included: age, using insulin as hypoglycemic medication, having past history of PTB before diabetic follow up initiation and alcoholic history while BMI was associated with a rate reduction of EPTB. Early screening and treatment for extra pulmonary tuberculosis is highly recommended at diabetes mellitus follow up for patients with the above risk factors.

Increased risk of pulmonary and extrapulmonary tuberculosis infection in patients with polycystic kidney disease: a nationwide population-based study with propensity score-matching analysis

BackgroundPolycystic kidney disease (PKD) is a common renal disorder affecting approximately 1 in 1000 live births. Tuberculosis (TB) is an infectious disease worldwide. This study investigated the risk of TB infection in patients with PKD.MethodsA nationwide population-based cohort study was performed using Taiwan’s National Health Insurance Research Database. We used patients’ hospitalization files for the entire analysis during 2000–2012. As per diagnosis, we divided patients into PKD and non-PKD cohorts and the major outcome was TB infection.ResultsA total of 13,540 participants with 6770 patients in each cohort were enrolled. The PKD cohort had a higher risk of TB infection than did the non-PKD cohort after adjusting for age, sex, and comorbidities (adjusted hazard ratio (aHR) = 1.91, 95% confidence interval [CI] = 1.51–2.43). When classifying by sites of pulmonary TB (PTB) and extrapulmonary TB (EPTB), the PKD cohort demonstrated a significantly higher risk of EPTB (aHR = 2.44, 95% CI = 1.46–4.08) as well as a risk of PTB (aHR = 1.69, 95% CI = 1.29–2.22). When stratified by the presence or absence of a comorbidity, high TB infection risk was noted in the PKD patients without any comorbidity (HR = 2.69, 95% CI = 1.69–4.30).ConclusionsTaken together, our findings suggest that PKD is associated with a 1.91-fold increased risk of TB infection. Medical professionls should maintain a high index of suspicion in daily practice for patients with PKD, particularly those with EPTB infection.

Association of IFN-gamma and IL-10 gene variants with the risk of extrapulmonary tuberculosis.

Tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB) is a chronic infectious disease. Interferon-gamma (IFN-γ) is an important cytokine imparting resistance to mycobacterial diseases. It is believed that IFN-γ and Interleukin-10 (IL-10) play divergent roles in the host immune system against MTB infection. IL-10 is an important inhibitory cytokine and helps balancing the inflammatory and immune responses. IL-10 is involved in down regulation of Th1 cytokines, MHC class II antigen and co-stimulatory molecular expression on macrophages, while IFN-γ results in macrophage activation allowing them to exert the microbicidal role. The objectives were to find out the association of IL-10 (−1082 A/G) and IFN-γ (+874 A/T) single nucleotide polymorphisms (SNPs) with extrapulmonary tuberculosis in ethnic Kashmiri population. A total of 100 extrapulmonary tuberculosis cases and 102 healthy controls were analyzed for IL-10 (−1082 A/G) and IFN- γ (+874 A/T) SNPs using Allele-Specific PCR. We found a significant association of IFN-γ + 874 ‘TT’ genotype with extrapulmonary tuberculosis (p = 0.006) and in case of IL-10 (−1082 A/G) we found a significant association with extrapulmonary tuberculosis under recessive model (GG vs GA + AA) (p = 0.03) in Kashmiri population. IL-10 (−1082 A/G) and IFN-γ (+874 A/T) have a significant association with extrapulmonary tuberculosis in ethnic Kashmiri population.

Recent epidemiological trends in extrapulmonary TB in Galicia, Spain.

OBJECTIVE: To describe the epidemiological trends and characteristics of extrapulmonary tuberculosis (EPTB) in Galicia, Spain, from 2000 to 2019.METHODS: This was a retrospective cohort study based on data from the Galician TB information system.RESULTS: Of the total number of TB cases (n = 15,871), 5,428 (34.2%) had EPTB. The absolute number of cases and incidence of EPTB decreased dramatically (from 480 cases and 17.8 cases/100,000 in 2000, to 172 and 6.4 cases/100,000 in 2019, respectively), with a mean annual decrease of respectively 64% and 4.7% for absolute cases and incidence rates. The risk for EPTB was higher in men than in women (RR 3.86, 95% CI 3.66-4.07). The most frequent age group was 15-44 years (2,234 patients, 41.2%); overall reductions per age group were 82% (0-14 years), 75% (15-44 years), 44% (45-64 years) and 63% (≥65 years), with statistically significant differences. The most frequently locations were the pleura (1,916 cases; 35.3%) and the lymph nodes (1,504; 27.7%).CONCLUSION: The incidence of EPTB in Galicia has decreased significantly in the last 20 years. The epidemiological characteristics have not changed, except for the number of patients with risk factors. This improvement of EPTB epidemiological trends coincides with the implementation of the programme for the prevention and control of TB, which suggests that it has been very effective in the control of the EPTB.

Single-Nucleotide Variants in the AIM2 - Absent in Melanoma 2 Gene (rs1103577) Associated With Protection for Tuberculosis.

Tuberculosis (TB) remains a serious public health burden worldwide. TB is an infectious disease caused by the Mycobacterium tuberculosis Complex. Innate immune response is critical for controlling mycobacterial infection. NOD-like receptor pyrin domain containing 3/ absent in melanoma 2 (NLRP3/AIM2) inflammasomes are suggested to play an important role in TB. NLRP3/AIM2 mediate the release of pro-inflammatory cytokines IL-1β and IL-18 to control M. tuberculosis infection. Variants of genes involved in inflammasomes may contribute to elucidation of host immune responses to TB infection. The present study evaluated single-nucleotide variants (SNVs) in inflammasome genes AIM2 (rs1103577), CARD8 (rs2009373), and CTSB (rs1692816) in 401 patients with pulmonary TB (PTB), 133 patients with extrapulmonary TB (EPTB), and 366 healthy control (HC) subjects with no history of TB residing in the Amazonas state. Quantitative Real Time PCR was performed for allelic discrimination. The SNV of AIM2 (rs1103577) is associated with protection for PTB (padj: 0.033, ORadj: 0.69, 95% CI: 0.49-0.97). CTSB (rs1692816) is associated with reduced risk for EPTB when compared with PTB (padj: 0.034, ORadj: 0.50, 95% CI: 0.27-0.94). Serum IL-1β concentrations were higher in patients with PTB than those in HCs (p = 0,0003). The SNV rs1103577 of AIM2 appeared to influence IL-1β release. In a dominant model, individuals with the CC genotype (mean 3.78 ± SD 0.81) appeared to have a higher level of IL-1β compared to carriers of the T allele (mean 3.45 ± SD 0.84) among the patients with PTB (p = 0,0040). We found that SNVs of AIM2 and CTSB were associated with TB, and the mechanisms involved in this process require further study.

Ethnicity based comprehensive evaluation of polymorphism in interferon-gamma gene and its association with pulmonary and extra-pulmonary tuberculosis risk: An updated trial sequential meta-analysis.

Host genetic background plays an important role in susceptibility to intracellular infectious pathogens like Mycobacterium tuberculosis (Mtb). Cellular immune response activation is vital for protection to these pathogens. Interferon-gamma (IFN-γ) plays a crucial role in this activation and preventing the intracellular growth of Mtb. A mutation in the IFN-γ gene, therefore, may lead to increased susceptibility to tuberculosis (TB) that may vary in different ethnic groups and its consequence also varies in pulmonary and extra-pulmonary TB (EPTB). Several IFN-γ gene polymorphisms are investigated for susceptibility to TB, but their associations are not always consistent as its impact may vary from one ethnicity to the other as well as with the type of TB. Hence, we performed a meta-analysis to overcome this problem. The present study involves comprehensive meta-analysis of + 874T/A polymorphism in the IFN-γ gene based on type of TB within five different ethnic groups to show its association with increased susceptibility to TB. Using PubMed and Google Scholar databases, a total of 50 case-control studies were retrieved having 8152 cases and 9755 controls in this meta-analysis. Thirty-eight studies of + 874T/A polymorphism of IFN-γ gene were correlated for Pooled odds ratios with 95% confidence intervals. The polymorphism was analyzed for six genetic models for five major ethnic groups accounting for heterogeneity among studies. Moreover, the sub-group analysis was based on the type of TB within each ethnic group. Trial sequential analysis was also performed for all the sub-groups to estimate the statistical consistency. IFN-γ +874 T/A polymorphism analysis clearly confirmed the increased association of + 874AA genotype with increased TB risk. This polymorphism also showed significant association in East Asian, European, American, and African ethnic groups whereas no such association was found in Asians. Patients with pulmonary TB (PTB) confirmed the association in East Asians, Africans, and Americans, whereas patients with EPTB showed association in Asian and East Asian populations only. This study reaffirms the association of IFN-γ+874 T/A polymorphism with TB risk. It specifically confirms that IFN-γ+874 T/A polymorphism increases the susceptibility of pulmonary infection in Africans and Americans, while the East Asian population is more susceptible to both, pulmonary and EPTB.

Withdrawal: Associations of tumor necrosis factor-α polymorphisms with the risk of tuberculosis: a meta-analysis.

Recently, the roles of tumor necrosis factor-α (TNF-α) polymorphisms in tuberculosis (TB) were intensively analyzed, but the results of these studies were inconsistent. Therefore, we performed this study to better assess the relationship between TNF-α polymorphisms and the risk of TB. Eligible studies were searched in PubMed, Medline, Embase and CNKI. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess correlations between TNF-α polymorphisms and TB. A total of 31 studies were included for analyses. Significant associations with the risk of TB were detected for TNF-α -308 G/A and -857 C/T polymorphisms in overall analyses. Further subgroup analyses based on ethnicity of participants revealed that TNF-α -238 G/A, -308 G/A, -857 C/T and -863 C/A polymorphisms were all significantly associated with the risk of TB in East Asians. When we stratified available data according to type of disease, we found that TNF-α -238 G/A and -308 G/A polymorphisms were significantly correlated with the risk of extrapulmonary tuberculosis (EPTB), while the -857 C/T polymorphism was significantly correlated with the risk of pulmonary tuberculosis (PTB). In conclusion, our findings indicated that TNF-α -238 G/A, -308 G/A, -857 C/T and -863 C/A polymorphisms may serve as potential biological markers for TB in East Asians. This article is protected by copyright. All rights reserved.

Genetic Polymorphisms of miR-149 Associated with Susceptibility to Both Pulmonary and Extrapulmonary Tuberculosis.

Background: Single nucleotide polymorphisms (SNPs) within precursor microRNAs (miRNAs) can affect the expression of the miRNAs and may be involved in the pathogenesis of pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB). Aims: We investigated the potential associations among four precursor miRNA SNPs (miR-149 A>G, C>T; miR-196a2 C>T; miR-499 C>T) and both PTB and EPTB. Methods: The study included 380 PTB patients, 242 EPTB patients, and 606 healthy control (HC) subjects from a Chinese Han population. We determined the miRNA relative expression levels from 10 HCs and 10 tuberculosis (TB) patients by quantitative PCR. Results: We found that the PTB group had a significantly lower miR-149 level (p < 0.05) versus the HCs. The allele and genotype frequencies of the miR-149 SNPs were significantly different between the TB patients and the HC group. The C allele at the rs2292832 and the A allele at the rs71428439 locus were associated with susceptibility to EPTB. The C allele of rs2292832 was associated with an increased risk of EPTB compared with that of HCs (p < 0.01), and the A allele of rs71428439 was protective against EPTB (p < 0.01) and PTB (p < 0.01). Conclusions: We identified genetic polymorphisms in miR-149 that appear to be associated with susceptibility to both PTB and EPTB within a Chinese population.

A trial sequential meta-analysis of IFN-γ +874 A>T (rs2430561) gene polymorphism and extrapulmonary tuberculosis risk

Interferon-γ (IFN-γ) plays a crucial role in immunological responses against Mycobacterium tuberculosis (M.tb) infection. The polymorphism at +874 A > T (rs2430561) influences the levels of IFN-γ, which may further influence the susceptibility to extrapulmonary tuberculosis (EPTB). This polymorphism has been investigated with respect to EPTB occurrence in different populations and provided contradictory and conflicting results. This study was performed to meta-statistically analyze the data and draw a more accurate conclusion regarding the association of IFN-γ +874 A > T gene polymorphism and EPTB susceptibility. A quantitative synthesis was executed for the pertinent studies retrieved from online web-databases viz. Google Scholar, PubMed/Medline and EMBASE. The pooled odds ratios (ORs) and confidence intervals (95% CIs) were estimated for all the genetic models by meta-analysis. A total of eight studies were retrieved which included 762 confirmed EPTB cases and 1341 controls. The meta-analysis results revealed reduced association of EPTB in allelic contrast (T vs. A: p = 0.001; OR = 0.668, 95% CI = 0.524 to 0.850), homozygous (TT vs. AA: p = 0.017; OR = 0.450, 95% CI = 0.234 to 0.868), heterozygous (AT vs. AA: p = 0.004; OR = 0.574, 95% CI = 0.395 to 0.835), dominant (TT + AT vs. AA: p = 0.003; OR = 0.536, 95% CI = 0.354 to 0.810) and recessive (TT vs. AA + AT: p = 0.039; OR = 0.662, 95% CI = 0.448 to 0.980) genetic models. Furthermore, re-sampling statistics also revealed reduced risk of EPTB in overall population and Asian subgroup. This meta-analysis concluded that IFN-γ +874 A > T gene polymorphism is meaningfully related with the reduced EPTB risk in overall and Asian population, and further necessitates larger studies to be conducted on this topic in other races.

Utility of Point-of-care Ultrasound in Children With Pulmonary Tuberculosis.

Point-of-care ultrasound (POCUS) detects extrapulmonary tuberculosis (EPTB) in HIV infected adults but has not been evaluated in children despite their higher risk of EPTB. This study's aims were to investigate feasibility of POCUS for EPTB in children, frequency of POCUS findings suggestive of EPTB and time to sonographic resolution of findings with treatment. This prospective South African cohort study enrolled children with suspected pulmonary tuberculosis (PTB). POCUS for pleural, pericardial or ascitic effusion, abdominal lymphadenopathy or splenic or hepatic microabscesses was performed and repeated at 1, 3 and 6 months of tuberculosis (TB) treatment. Prevalence of POCUS findings and their association with HIV infection was investigated in children with confirmed PTB (microbiologically proven), unconfirmed PTB (clinically diagnosed) or unlikely TB (respiratory disease that improved during follow-up without TB treatment). Of 232 children [median age 37 months (interquartile range, 18-74)], 39 (17%) were HIV infected. Children with confirmed or unconfirmed PTB had a higher prevalence of POCUS findings than children with unlikely TB [18 of 58 (31%) and 36 of 119 (30%) vs. 8 of 55 (15%); P = 0.04 and P = 0.03, respectively]. Pleural effusion [n = 30 (13%)] or abdominal lymphadenopathy [n = 28 (12%)] were the most common findings; splenic microabscesses [n = 12 (5%)] were strongly associated with confirmed PTB. Children coinfected with HIV and TB were more likely than HIV-uninfected children with TB to have abdominal lymphadenopathy (37% vs. 10%; P < 0.001) or splenic microabscesses (23% vs. 3%; P < 0.001]. Most ultrasound findings were resolved by 3 months with appropriate TB treatment. POCUS for EPTB in children with PTB is feasible. The high prevalence of findings suggests that POCUS can contribute to timely diagnosis of childhood TB and to monitoring treatment response.

Analysis of extrapulmonary tuberculosis in Spain: 2007–2012 National Study

IntroductionThis study sought to study the epidemiological characteristics of the extrapulmonary tuberculosis (EPTB) in relation to pulmonary tuberculosis (PTB) from 2007 to 2012 in Spain, and plot its trend across the same period. MethodsWe conducted an analytical cross-sectional study in which the following variables were analysed: age; sex; disease site; history of antituberculosis treatment; country of birth; presence of HIV infection; and culture results. Age-related differences were ascertained using the test of comparison of proportions, and crude and adjusted ORs were calculated using linear regression models. ResultsOf the total of 44,050 cases of tuberculosis reported in the period 2007–2012 and included in the study, 31,508 (71.53%) were pulmonary tuberculosis and 12,542 (28.47%) were EPTB. EPTB rates decreased across all age groups. The main EPTB risk factor was presence of HIV infection (OR 1.39). Persons aged under 65 years had a lower risk of EPTB. ConclusionsAlthough persons aged over 65 years displayed the highest incidence, there was nevertheless a downward trend across all age groups. Whereas children showed a significant decrease in tuberculous meningitis, this was not so for all extrapulmonary forms. EPTB rates among persons born outside Spain were much higher than those among the Spanish population.

Association of HIV infection with extrapulmonary tuberculosis: a systematic review.

HIV/AIDS is a known risk factor for the development of pulmonary tuberculosis (PTB). However, the association is less clear between HIV and extrapulmonary tuberculosis (EPTB). We conducted a systematic review to determine the association between HIV and EPTB. We searched the electronic databases Medline, Embase, and relevant conference literature using defined search terms for EPTB and HIV. Only publications in English and only studies reporting adjusted estimates were included, while our search criteria did not include restriction by age or geographic location of study participants. Qualitative and quantitative analyses (including I 2 test for heterogeneity) were performed. Sixteen studies (15 cross-sectional and 1 case-control) conducted from 1984 to 2016 were included in the final analyses after screening 5163 articles and conference abstracts. Our qualitative analysis showed heterogeneity in study design and study population characteristics along with a medium/high risk of bias in the majority of studies. While most of the individual studies showed increased odds of EPTB compared with PTB among HIV-infected individuals, we did not provide an overall pooled estimate, as the I 2 value was high at 93% for the cross-sectional studies. While an association between HIV and EPTB is observed in most individual studies, the high heterogeneity and risk of bias in these studies highlight the need for further well-designed prospective cohort studies to assess the true risk of EPTB in the HIV-infected patient population.

P2X71513 A>C Polymorphism Confers Increased Risk of Extrapulmonary Tuberculosis: A Meta-analysis of Case-Control Studies.

The association of A1513C (rs3751143) polymorphism of P2X7 gene with the risk of extrapulmonary tuberculosis (EPTB) has been extensively analyzed, but no consensus has been achieved. In this study, a meta-analysis was done to assess this precise association. Online web databases, like PubMed (MEDLINE) and EMBASE were searched for pertinent reports showing association of P2X7 A1513C polymorphism with EPTB risk. To assess the strength of this association, we calculated pooled odds ratios (ORs) and 95% confidence intervals (95% CIs). A total of eight reports involving 2237controls and 594 EPTB cases were included in this study. Four genetic models, viz. allele (C vs. A: p=0.011; OR= 1.677, 95% CI = 1.125–2.501), homozygous (CC vs. AA: p = 0.053; OR= 2.362, 95% CI = 0.991–5.632), heterozygous (AC vs. AA: p = 0.003; OR= 1.775, 95% CI = 1.209–2.607) and dominant (CC + AC vs. AA: p = 0.005; OR= 1.890, 95% CI = 1.207–2.962) showed significant associations compared with wild type genotypes. Subgroup analysis stratified by ethnicity was also performed and the results suggested that homozygous and heterozygous genotypes were associated significantly with increased susceptibility of EPTB in Asian population. Similarly, heterozygous and dominant models showed increased EPTB risk in Caucasian population. The present meta-analysis suggests that P2X7 A1513C polymorphism may be an important risk factor for EPTB. Also, our sub-group analysis indicates that P2X7 A1513C polymorphism confers increased EPTB risk among Asians and Caucasians. However, future larger studies are needed to provide more precise conclusion and endorse the present results.

Analysis of extrapulmonary tuberculosis in Spain: 2007–2012 National Study

IntroductionThis study sought to study the epidemiological characteristics of the extrapulmonary tuberculosis (EPTB) in relation to pulmonary tuberculosis (PTB) from 2007 to 2012 in Spain, and plot its trend across the same period. MethodsWe conducted an analytical cross-sectional study in which the following variables were analysed: age; sex; disease site; history of antituberculosis treatment; country of birth; presence of HIV infection; and culture results. Age-related differences were ascertained using the test of comparison of proportions, and crude and adjusted ORs were calculated using linear regression models. ResultsOf the total of 44,050 cases of tuberculosis reported in the period 2007–2012 and included in the study, 31,508 (71.53%) were pulmonary tuberculosis and 12,542 (28.47%) were EPTB. EPTB rates decreased across all age groups. The main EPTB risk factor was presence of HIV infection (OR 1.39). Persons aged under 65 years had a lower risk of EPTB. ConclusionsAlthough persons aged over 65 years displayed the highest incidence, there was nevertheless a downward trend across all age groups. Whereas children showed a significant decrease in tuberculous meningitis, this was not so for all extrapulmonary forms. EPTB rates among persons born outside Spain were much higher than those among the Spanish population.

Burden of tuberculosis at post mortem in inpatients at a tertiary referral centre in sub-Saharan Africa: a prospective descriptive autopsy study

Patients with subclinical tuberculosis, smear-negative tuberculosis, extrapulmonary tuberculosis, multidrug-resistant tuberculosis, and asymptomatic tuberculosis are difficult to diagnose and may be missed at all points of health care. We did an autopsy study to ascertain the burden of tuberculosis at post mortem in medical inpatients at a tertiary care hospital in Lusaka, Zambia. Between April 5, 2012, and May 22, 2013, we did whole-body autopsies on inpatients aged at least 16 years who died in the adult inpatient wards at University Teaching Hospital, Lusaka, Zambia. We did gross pathological and histopathological analysis and processed lung tissues from patients with tuberculosis through the GeneXpert MTB/RIF assay to identify patients with multidrug-resistant tuberculosis. The primary outcome measure was specific disease or diseases stratified by HIV status. Secondary outcomes were missed tuberculosis, multidrug-resistant tuberculosis, and comorbidities with tuberculosis. Data were analysed using Pearson χ(2), the Mann-Whitney U test, and binary logistic regression. The median age of the 125 included patients was 35 years (IQR 29-43), 80 (64%) were men, and 101 (81%) were HIV positive. 78 (62%) patients had tuberculosis, of whom 66 (85%) were infected with HIV. 35 (45%) of these 78 patients had extrapulmonary tuberculosis. The risk of extrapulmonary tuberculosis was higher among HIV-infected patients than among uninfected patients (adjusted odds ratio 5·14, 95% CI 1·04-24·5; p=0·045). 20 (26%) of 78 patients with tuberculosis were not diagnosed during their life and 13 (17%) had undiagnosed multidrug-resistant tuberculosis. Common comorbidities with tuberculosis were pyogenic pneumonia in 26 patients (33%) and anaemia in 15 (19%). Increased clinical awareness and more proactive screening for tuberculosis and multidrug-resistant tuberculosis in inpatient settings is needed. Further autopsy studies are needed to ascertain the generalisability of the findings. UBS Optimus Foundation, EuropeAID, and European Developing Countries Clinical Trials Partnership (EDCTP).

Evaluation of health-care providers’ knowledge of childhood tuberculosis in Lima, Peru

Background:As most national tuberculosis programmes (NTPs) focus on adult tuberculosis (TB), NTP providers may not appreciate differences in the pathophysiology and presentation of childhood TB.Objectives:This study aimed to identify strengths and weaknesses in knowledge of childhood TB among the 326 NTP providers in Lima Ciudad and Lima Este—two of the Peruvian capital’s four health districts.Methods:310 providers—103 physicians, 106 nurses, 101 nursing technicians—accepted personal invitations to complete self-administered surveys, which included 14 childhood TB questions grouped into five sections: transmission, symptoms, diagnosis, prevention and treatment. Physicians were asked ten additional questions targeting their NTP diagnostic and management responsibilities.Results:All three groups scored 97–99% on the transmission section and 83–85% on the treatment section; however, no group scored above 66% on any other section. Fewer than 50% of nurses and technicians recognised young children’s high risk of extrapulmonary TB, extrapulmonary TB symptoms or the causes of false negative tuberculin skin tests. Twenty-three per cent of physicians correctly identified gastric aspirate culture sensitivity, and 42% the radiographical findings of pulmonary TB. Less than two-thirds of providers recognised the definition of latent TB infection (LTBI), young children’s high risk of progression from LTBI to disease or indications for isoniazid preventive therapy.Conclusions:Providers at the frontline of Peru’s TB control efforts demonstrated weaknesses in the areas of extrapulmonary disease, diagnosis and prevention. These knowledge gaps are likely to have resulted in delayed or missed diagnoses and lost opportunities for prevention. Educational interventions targeting NTP personnel may improve childhood TB care and outcomes.