Pulmonary involvement in patients presenting with extra-pulmonary tuberculosis: thinking beyond a normal chest x-ray

Assessment of the prevalence of pulmonary involvement in cases with extrapulmonary tuberculosis

Background:Concurrent pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) is associated with poor treatment outcomes yet its epidemiology in Uganda is unknown. The purpose of this study was to determine the prevalence, associated factors, and treatment outcomes of concurrent PTB and EPTB among patients at a national tuberculosis (TB) treatment center located at Mulago National Referral Hospital in Kampala, Uganda.Methods:We conducted a retrospective review of charts for people with TB who were enrolled in care between January 2015 and December 2019. Eligible charts were for people with pulmonary bacteriologically confirmed TB enrolled into care in the period under study. Concurrent PTB and EPTB was defined as PTB and bacteriological, histopathological, and/or radiological features of TB at another noncontiguous sites.Results:Overall, 400 patient charts were eligible, of whom 240 (60.0%) were aged 15–34 years and 205 (51.3%) were female. The prevalence of concurrent PTB and EPTB was 8.5% (34/400) [95% confidence interval (CI): 6.0–11.7%]. People with concurrent PTB and EPTB were more likely to have at least one comorbidity (82.4% versus 37.2%, p < 0.001), of which HIV was the most frequent. Furthermore, people with concurrent PTB and EPTB were more likely to have empyema (15% versus 2.6%, p = 0.028) but less likely to have bronchopneumonic opacification (0.0% versus 15.3%, p = 0.043) on chest x-ray imaging. People with concurrent PTB and EPTB had higher mortality (26.5% versus 6.37%) and a lower cure rate (41.2% versus 64.8%), p = 0.002.Conclusion:Our findings highlight the need for early detection of TB before dissemination particularly among people who use alcohol and people with HIV.

There is a high burden of both diabetes (DM) and tuberculosis (TB) in China, and as DM increases the risk of TB and adversely affects TB treatment outcomes, there is a need for bidirectional screening of the two diseases. How this is best performed is not well determined. In this pilot project in China, we aimed to assess the feasibility and results of screening DM patients for TB within the routine healthcare setting of five DM clinics. Agreement on how to screen, monitor and record was reached in May 2011 at a national stakeholders meeting, and training was carried out for staff in the five clinics in July 2011. Implementation started in September 2011, and we report on 7 months of activities up to 31 March 2012. DM patients were screened for TB at each clinic attendance using a symptom-based enquiry, and those positive to any symptom were referred for TB investigations. In the three quarters, 72% of 3174 patients, 79% of 7196 patients and 68% of 4972 patients were recorded as having been screened for TB, resulting in 7 patients found who were already known to have TB, 92 with a positive TB symptom screen and 48 of these newly diagnosed with TB as a result of referral and investigation. All patients except one were started on anti-TB treatment. TB case notification rates in screened DM patients were several times higher than those of the general population, were highest for the five sites combined in the final quarter (774/100 000) and were highest in one of the five clinics in the final quarter (804/100 000) where there was intensive in-house training, special assignment of staff for screening and colocation of services. This pilot project shows that it is feasible to carry out screening of DM patients for TB resulting in high detection rates of TB. This has major public health and patient-related implications.

Tuberculosis is a leading cause of death in developing countries where HIV is endemic. This hospital based study was done to estimate the magnitude of pulmonary and extra-pulmonary tuberculosis and to determine predictors of tuberculosis among febrile adults admitted at Bugando Medical Centre (BMC), Mwanza, Tanzania. A total of 346 adults febrile patients admitted in medical wards were studied. Sputum for AFB microscopy and chest X-rays was used to diagnose tuberculosis. Clinical features were collected using standardized data collection tool. HIV testing and CD4 counts were determined. Data were analyzed using STATA version 11 software. Of 346 febrile adults patients 116 (33.5%) were diagnosed to have tuberculosis; of which 79 (68.1%) and 37 (31.9%) had pulmonary tuberculosis (PTB) and extra-pulmonary tuberculosis, respectively. Smear negative PTB were more common in HIV positive than in HIV negative patients (50% vs. 18.5%, p=0.007). Extra-pulmonary tuberculosis was more common in HIV positive patients than pulmonary tuberculosis (86.4% vs. 13.6%), p=0.000 1). On multivariate logistic regression analysis the predictors of tuberculosis were; age above 35 years (OR =2.38, p=0.007), cardinal symptoms (OR=37, p<0.0001), pleural effusion (OR=24, p=0.0001), and HIV status (OR =3.2, p=0.0001). Of 79 patients with PTB, 48 (60.7%) were AFB smear positive and 31 (39.3%) were AFB smear negative. HIV patients with smear negative tuberculosis had significantly lower CD4 count than IV patients with smear positive tuberculosis (63.5 cells/µl versus 111.5 cells/µl) [Mann-Whitney test p=0.0431]]. No different in mortality was observed between patients with TB and those without TB admitted in BMC medical wards (28.5% vs. 23.0%, p= 0.13 18). Tuberculosis is the commonest cause of fever among adults patients admitted at BMC and is predicted by age above 35 years, positive HIV status, cardinal PTB symptoms, and pleural effusion. Routinely TB screening is highly recommended among adults with fever, cough, night sweating and wasting in countries where HIV is endemic.

Pediatric tuberculosis (TB) is a serious infectious disease that affects many children worldwide and is more likely to be extrapulmonary than adult TB. However, the clinical and epidemiological profile, and cost burden of pediatric extrapulmonary TB (EPTB) in China remain unknown. Here, we conducted a descriptive, multicenter study of pediatric TB patients from 22 hospitals across all six regions in China from October 2015 to December 2018. Of 4,654 patients, 54.23% (2,524) had pulmonary TB (PTB), 17.76% (827) had EPTB, and 28.00% (1,303) had concurrent extrapulmonary and pulmonary TB (combined TB). Compared with PTB, EPTB and combined TB were associated with lower hospitalization frequency (2.43 and 2.21 vs. 3.16 times), longer length of stay (10.61 and 11.27 vs. 8.56 days), and higher rate of discharge against medical advice (8.46% and 9.44% vs. 5.67%). EPTB was associated with higher mortality (0.97% vs. 0.24% and 0.31%), higher rate of low birth weight (17.69% vs. 6.79% and 6.22%), worse diagnosis at the first visit (21.16% vs. 34.67% and 44.47%), and worse hospitalization plan situation (4.35% vs. 7.81% and 7.44%), compared with PTB and combined TB. EPTB and combined TB had higher financial burdens (17.67% and 16.94% vs. 13.30%) and higher rates of catastrophic expenditure (8.22% and 9.59% vs. 5.03%), compared with PTB. Meningitis TB (34.18%) was the most frequent form of total extrapulmonary infection and had the highest cost burden and rate of catastrophic expenditure. In conclusion, improved screening approaches for pediatric EPTB are needed to reduce diagnostic challenges and financial burden.

BackgroundThe diagnosis of pulmonary tuberculosis in patients with Human Immunodeficiency Virus (HIV) is complicated by the increased presence of sputum smear negative tuberculosis. Diagnosis of smear negative pulmonary tuberculosis is made by an algorithm recommended by the National Tuberculosis and Leprosy Programme that uses symptoms, signs and laboratory results.The objective of this study is to determine the sensitivity and specificity of the tuberculosis treatment algorithm used for the diagnosis of sputum smear negative pulmonary tuberculosis.MethodsA cross-section study with prospective enrollment of patients was conducted in Dar-es-Salaam Tanzania. For patients with sputum smear negative, sputum was sent for culture. All consenting recruited patients were counseled and tested for HIV. Patients were evaluated using the National Tuberculosis and Leprosy Programme guidelines and those fulfilling the criteria of having active pulmonary tuberculosis were started on anti tuberculosis therapy. Remaining patients were provided appropriate therapy. A chest X-ray, mantoux test, and Full Blood Picture were done for each patient. The sensitivity and specificity of the recommended algorithm was calculated. Predictors of sputum culture positive were determined using multivariate analysis.ResultsDuring the study, 467 subjects were enrolled. Of those, 318 (68.1%) were HIV positive, 127 (27.2%) had sputum culture positive for Mycobacteria Tuberculosis, of whom 66 (51.9%) were correctly treated with anti-Tuberculosis drugs and 61 (48.1%) were missed and did not get anti-Tuberculosis drugs. Of the 286 subjects with sputum culture negative, 107 (37.4%) were incorrectly treated with anti-Tuberculosis drugs. The diagnostic algorithm for smear negative pulmonary tuberculosis had a sensitivity and specificity of 38.1% and 74.5% respectively. The presence of a dry cough, a high respiratory rate, a low eosinophil count, a mixed type of anaemia and presence of a cavity were found to be predictive of smear negative but culture positive pulmonary tuberculosis.ConclusionThe current practices of establishing pulmonary tuberculosis diagnosis are not sensitive and specific enough to establish the diagnosis of Acid Fast Bacilli smear negative pulmonary tuberculosis and over treat people with no pulmonary tuberculosis.

BACKGROUND AND OBJECTIVES:There are few reports of cutaneous tuberculosis with immunosuppressed states such as HIV, use of immunosuppressants or malignancy. Diagnosis is thus difficult and despite scientific advances such as polymerase chain reaction, it is frequently missed. Although rare, given its worldwide prevalence and the rising incidence of HIV, it is important for clinicians to recognize the variants and promptly treat the patient.DESIGN AND SETTING:Retrospective study of all cases of cutaneous tuberculosis diagnosed from October 2007 to November 2009 at an outpatient clinic of a tertiary-care hospital in northern India.METHODS:We collected information on the clinical form of disease, histopathology and HIV concurrence rates and looked for differences in presentation between mmunocompetent and immunocompromised states. We also looked for differences and HIV concurrence between immunocompetent and immunocomprised patients. Diagnosis was based on clinical, histopathological and microbiological tests for tuberculosis and a test for HIV.RESULTS:The overall incidence of cutaneous tuberculosis was 0.7% (131 of 18720 outpatients). HIV concurrence was 9.1% (12 cases) of all cutaneous tuberculosis cases. Most common variants seen were scrofuloderma (36.5%), lupus vulgaris (31%), tuberculosis verruca cutis (12.9%), lichen scrofulosorum (11.4%), papulonecrotic tuberculids (3.8%), erythema nodosum (2.2%) and erythema induratum of Bazin (1.5%).CONCLUSIONS:Cutaneous tuberculosis rates were slightly higher in our study than in other studies from India. HIV co-infection rates were similar to those in other studies. Many atypical morphological forms and presentations were observed in HIV co-infected patients. Due to the varied clinical presentations, physician awareness and a high index of suspicion are necessary to diagnose cutaneous forms of tuberculosis.

Extrapulmonary tuberculosis (EPTB) poses a public health challenge, particularly among individuals with human immunodeficiency virus (HIV). However, many EPTB cases arise in those without HIV, leaving the underlying factors unclear. This study aims to characterize patients with pulmonary tuberculosis (PTB) and EPTB, exploring the differences in associated factors for each type in patients with and without HIV. An analytical observational study was conducted on a cohort of tuberculosis (TB) patients diagnosed between 2014 and 2021 in a referral hospital in Bogotá, Colombia. Patients were categorized into PTB or EPTB based on the site of infection. Data on demographic and clinical variables were collected, comparing the two groups. A multivariate logistic regression model was created to identify factors associated with EPTB compared to PTB. The study encompassed 533 patients: 310 with PTB and 223 with EPTB, of which only 65 (14.7%) were HIV positive. PTB patients exhibited higher rates of active smoking, smoking cessation, diabetes mellitus (DM), and other pulmonary diseases. The logistic regression identified HIV infection as the only factor associated with EPTB (OR 2.36 (1.54-3.61), p < 0.001). Conversely, quitting smoking (OR 0.58 (0.35-0.96) p = 0.038), DM (OR 0.41 (0.21-0.82) p = 0.011), chronic obstructive pulmonary disease (COPD) (OR 0.18 (0.08-0.4) p < 0.001), other pulmonary diseases (OR 0.21 (0.61-0.77) p = 0.019), or those using immunosuppressants (OR 0.44 (0.20-0.96) p = 0.04) exhibited a negative association with EPTB compared to PTB. Specific models for pleural and lymph node TB revealed distinct associations, with HIV strongly linked to lymph node TB (OR 3.38, 95% CI 1.57-7.26, p = 0.002). EPTB is primarily associated with HIV infection, while smoking, DM, COPD, other pulmonary diseases, and immunosuppressant use are associated with PTB. Variability in associated factors for specific EPTB forms underlines the need for tailored research into the predisposing factors for EPTB, particularly in HIV-negative patients.

Smear-Negative Pulmonary Tuberculosis in Industrialized Countries

Background: Tuberculosis (TB) is a serious global public health problem and is the second most common cause of death from infectious disease. The aim of this study was to assess trends of TB and treatment outcomes in the past four years in Mizan Aman General Hospital, Southwestern Ethiopia. Methods: We analyzed the records of 2150 tuberculosis patients registered at Mizan Aman General Hospital from June 2010 to July 2013. Tuberculosis type and treatment outcome were categorized according to the national tuberculosis control program guideline. Data analysis was performed using the statistical package SPSS for windows, version 20. Results: From the total of 2150 TB patients registered during the indicated period, 2090 (97.2%) were new cases and 60 (2.8%) were re-treated cases. Of which, 1125 (52.3%) were smear negative pulmonary TB (SNPTB) cases and the rest, 532 (24.7%) and 493 (23%) were smear positive pulmonary TB (SPPTB) and extra pulmonary TB (EPTB) cases respectively. Trends of all forms of TB increased from 363 in 2010 to 634 in 2011, and decreased in the year 2012 (330), and then, increased in the year 2013 (823). Regarding treatment outcomes, 561 (26.1%) were successfully treated, 26 (1.2%) defaulted, 49 (2.3%) died, and 1514(70.4%) patients were transferred out. Age and year of enrollment of TB patients were associated with higher treatment success (P<0.05). On the other hand, patient category, HIV status and year of enrollment of TB patients were significantly associated with death rate (P<0.05). Conclusion: TB in the hospital showed a fluctuating pattern for the last four years and the proportion of SNPTB cases was highest compared to cases of SPPTB and EPTB. The treatment success of all types of TB was unsatisfactory, which is a serious public health concern that needs to be addressed.

BackgroundTuberculosis (TB) and human immunodeficiency virus (HIV) co-infection is a major source of morbidity and mortality globally. The World Health Organization (WHO) has recommended that HIV counselling and testing be offered routinely to TB patients in order to increase access to HIV care packages. We assessed the uptake of provider-initiated testing and counselling (PITC), antiretroviral (ART) and co-trimoxazole preventive therapies (CPT) among TB patients in the Northwest Region, Cameroon.MethodsA retrospective cohort study using TB registers in 4 TB/HIV treatment centres (1 public and 3 faith-based) for patients diagnosed with TB between January 2006 and December 2007 to identify predictors of the outcomes; HIV testing/serostatus, ART and CPT enrolment and factors that influenced their enrolment between public and faith-based hospitals.ResultsA total of 2270 TB patients were registered and offered pre-HIV test counselling; 2150 (94.7%) accepted the offer of a test. The rate of acceptance was significantly higher among patients in the public hospital compared to those in the faith-based hospitals (crude OR 1.97; 95% CI 1.33 - 2.92) and (adjusted OR 1.92; 95% CI 1.24 - 2.97). HIV prevalence was 68.5% (1473/2150). Independent predictors of HIV-seropositivity emerged as: females, age groups 15-29, 30-44 and 45-59 years, rural residence, previously treated TB and smear-negative pulmonary TB. ART uptake was 50.3% (614/1220) with 17.2% (253/1473) of missing records. Independent predictors of ART uptake were: previously treated TB and extra pulmonary TB. Finally, CPT uptake was 47.0% (524/1114) with 24% (590/1114) of missing records. Independent predictors of CPT uptake were: faith-based hospitals and female sex.ConclusionPITC services are apparently well integrated into the TB programme as demonstrated by the high testing rate. The main challenges include improving access to ART and CPT among TB patients and proper reporting and monitoring of programme activities.

Effect of glycemic control on lymphocyte subsets in the dissemination of pulmonary tuberculosis: A retrospective analysis

Background: Tuberculosis (TB) infection is thought to develop at any stage of HIV infection. Pulmonary tuberculosis (PTB) and extra-pulmonary tuberculosis are major complications in HIV/AIDS patients. Tuberculosis is still a diagnostic dilemma in low resource countries, with approximately 68.4% of all active pulmonary cases being negative for AAFBs on sputum. Additionally, it is reported that 46.7% of the active cases have disseminated TB with extra-pulmonary TB; further complicating the diagnosis in post-conflict northern Uganda. We therefore sought to clinically and radiologically characterize the various TB diagnosed in HIV/AIDS patients in this low resource and post conflict environment. Materials and Methods: A prospective cohort study was conducted on 320 sero-positive patients in Lacor Hospital. Clinical features, radiographic and ultrasonographic features of confirmed HIV sero-positive patients with suspected TB co-infection were assessed. Patients were recruited consecutively and the Chest radiographs, thoraco-lumbar and lumbar spine radiographs were taken and analyzed. Trans-thoracic ultrasonography (USS) for justified cases with pleural and pericardial effusion was conducted. FNAB and Tru-cut biopsies were performed for histological confirmation. Cases were followed-up for clinical outcomes (improvement and demise) within 2 months. The ethics and review committee of Gulu University Medical School approved the study and patients who did not meet the inclusion criteria were excluded. Data was analyzed using SPSS 13.0. Results: Atypical Chest x-ray finding included: reticulo-nodular infiltrates (69.7%); hilar and mediastinal adenopathy (40%); pleural effusion (27.5%) and miliary (20.6%). Typical Chest x-ray finding included: Apical reticulo-nodularities and fibro-cavitations (27.5%), and normal Chest x-ray (2.2%). Abdominal Ultrasonographic finding included: porta-hepatis, para-aortic and splenic hilum lymphadenopathy (15.9%); Ascitis (8.1%); TB splenitis (5.3%) and TB nephritis with peri-renal abscess (0.3%). PTB was observed in (53.4%); disseminated TB in (42.2%) and EPTB in (4.4%). Majority (81.9%) of the patients improved and was discharged on DOTS while 18.1% died. Conclusion: Imaging assessment is important adjuvant in HIV/AIDS/TB co-epidemic diagnosis. Early diagnosis and prompt management of TB co-infection ensures longer life and reduce morbidity and mortality.

Tuberculosis in health care workers in Malawi

The steadily growing epidemic of diabetes mellitus poses a threat for global tuberculosis (TB) control. Previous studies have identified an important association between diabetes mellitus and TB. However, these studies have limitations: very few were carried out in low-income countries, with none in Africa, raising uncertainty about the strength of the diabetes mellitus-TB association in these settings, and many critical questions remain unanswered. An expert meeting was held in November 2009 to discuss where there was sufficient evidence to make firm recommendations about joint management of both diseases, to address research gaps and to develop a research agenda. Ten key research questions were identified, of which 4 were selected as high priority: (i) whether, when and how to screen for TB in patients with diabetes mellitus and vice versa; (ii) the impact of diabetes mellitus and non-diabetes mellitus hyperglycaemia on TB treatment outcomes and deaths, and the development of strategies to improve outcomes; (iii) implementation and evaluation of the tuberculosis 'DOTS' model for diabetes mellitus management; and (iv) the development and evaluation of better point-of-care diagnostic and monitoring tests, including measurements of blood glucose and glycated haemoglobin A(1c) (HbA(1c)) for patients with diabetes mellitus. Implementation of this research agenda will benefit the control of both diseases.