Search

Introduction: Tuberculosis (TB) is an important cause of morbidity and mortality among people living with HIV (PLHIV). Current WHO-recommended strategies for diagnosing TB among hospitalized PLHIV rely on symptom screening and disease severity to assess eligibility for urine lipoarabinomannan lateral flow (LF-LAM) and molecular testing. Despite these recommendations, autopsy studies show a large burden of undiagnosed TB among admitted PLHIV. The EXULTANT trial aims to assess the impact of an expanded screening strategy using three specimens (sputum, stool, and urine) for TB diagnosis among PLHIV admitted to hospitals in two high HIV and TB burden African countries. Methods: This is a multicenter, pragmatic, individually randomized controlled trial conducted across eleven hospitals in Tanzania and Mozambique. Participants in the intervention arm will be tested with Xpert MTB/RIF Ultra® from expectorated sputum, stool, and urine samples, with additional urine LF-LAM testing in the first 24 h after hospital admission, irrespective of the presence of the symptoms. The control arm will implement the WHO standard of care recommendations. Hospitalized adults (≥ 18 years) with a confirmed HIV-diagnosis, irrespective of antiretroviral (ART) therapy status or presence of TB symptoms will be assessed for eligibility at admission. Patients with a pre-existing TB diagnosis, those receiving anti-tuberculosis therapy or tuberculosis preventive treatment in the 6 months prior to enrolment, and those transferred from other hospitals will not be eligible. Also, participants admitted for traumatic reasons such as acute abdomen, maternal conditions, scheduled surgery, having a positive SARS-CoV2 test will be ineligible. The primary endpoint is the proportion of participants with microbiologically confirmed TB starting treatment within 3 days of enrolment. Discussion: The EXULTANT trial investigates rapid implementation after admission of a new diagnostic algorithm using Xpert MTB/RIF Ultra® in several non-invasive specimens, in addition to LF-LAM, in hospitalized PLHIV regardless of TB symptoms. This enhanced strategy is anticipated to detect frequently missed TB cases in this population and is being evaluated as an implementable and scalable intervention. Trial registration: Trial reference number: NCT04568967 (ClinicalTrials.gov) registered on 2020–09-29. [ABSTRACT FROM AUTHOR]

Background: In 2022, fewer than half of persons with tuberculosis (TB) had access to molecular diagnostic tests for TB due to their high costs. Studies have found that the use of artificial intelligence (AI) software for chest X-ray (CXR) interpretation and sputum specimen pooling can each reduce the cost of testing. We modeled the combination of both strategies to estimate potential savings in consumables that could be used to expand access to molecular diagnostics. Methods: We obtained Xpert testing and positivity data segmented into deciles by AI probability scores for TB from the community- and healthcare facility-based active case finding conducted in Bangladesh, Nigeria, Viet Nam, and Zambia. AI scores in the model were based on CAD4TB version 7 (Zambia) and qXR (all other countries). We modeled four ordinal screening and testing approaches involving AI-aided CXR interpretation to indicate individual and pooled testing. Setting a false negative rate of 5%, for each approach we calculated additional and cumulative savings over the baseline of universal Xpert testing, as well as the theoretical expansion in diagnostic coverage. Results: In each country, the optimal screening and testing approach was to use AI to rule out testing in deciles with low AI scores and to guide pooled vs individual testing in persons with moderate and high AI scores, respectively. This approach yielded cumulative savings in Xpert tests over baseline ranging from 50.8% in Zambia to 57.5% in Nigeria and 61.5% in Bangladesh and Viet Nam. Using these savings, diagnostic coverage theoretically could be expanded by 34% to 160% across the different approaches and countries. Conclusions: Using AI software data generated during CXR interpretation to inform a differentiated pooled testing strategy may optimize TB diagnostic test use, and could extend molecular tests to more people who need them. The optimal AI thresholds and pooled testing strategy varied across countries, which suggests that bespoke screening and testing approaches may be needed for differing populations and settings. [ABSTRACT FROM AUTHOR]

Background: Most cases of chronic empyema are caused by acute thoracic empyema or tuberculous pleuritis. Open thoracotomy and decortication are traditional treatments for chronic empyema. However, some cases, such as those with thick calcifications around a large cavity, may be difficult to decorticate in a single surgery. We successfully treated a case of chronic empyema with a large cavity surrounded by a thick calcified membrane that was peeled off gradually each day through fenestration of the thoracic cavity with negative-pressure wound therapy (NPWT). Case presentation: The patient was a 47-year-old man who had undergone thoracic drainage for left post-pneumonia empyema at another hospital 10 years previously. He presented to our hospital with a fever of 39 °C, bloody sputum, and severe fatigue for 3 days. Computed tomography showed a 9-cm mass shadow in the left intralobar space and an adjacent 21 × 15 × 9-cm fluid-filled calcified unilocular cavity up to 5 mm in thickness. He underwent thoracic drainage for fluid, and empyema was suspected; the fluid was foul-smelling and purulent. The patient did not improve with antibiotics and intrathoracic lavage; therefore, thoracoscopic decortication was performed. The thoracic cavity had a thick calcified membrane filled with dark-red slurry resembling old blood. We attempted decortication; however, the calcified membrane was difficult to remove. Two drains were used for the pleural lavage. However, no improvement was observed with intrathoracic lavage and drainage; therefore, a fenestration was performed. The calcified membrane was peeled off each day for 3 months. Gradually, granulation increased and the inflammatory reaction improved. After NPWT, the empyema cavity gradually shrank to 8 cm × 6 cm × 2 cm. A latissimus dorsi flap closure was performed, and the patient was discharged. Conclusions: This is an informative report on the daily decortication of a highly calcified purulent membrane using NPWT in a patient with chronic empyema. The description of this method will aid in the management of patients with chronic empyema and thick calcified membranes. [ABSTRACT FROM AUTHOR]

Background: In 2020, the WHO-approved Molbio Truenat platform and MTB assays to detect Mycobacterium tuberculosis complex (MTB) and resistance to rifampicin directly on sputum specimens. This primary health care center-based trial in Mozambique and Tanzania investigates the effect of Truenat platform/MTB assays (intervention arm) combined with rapid communication of results compared to standard of care on TB diagnosis and treatment initiation for microbiologically confirmed TB at 7 days from enrolment. Methods: The Tuberculosis Close the Gap, Increase Access, and Provide Adequate Therapy (TB-CAPT) CORE trial employs a pragmatic cluster randomized controlled design to evaluate the impact of a streamlined strategy for delivery of Truenat platform/MTB assays testing at primary health centers. Twenty-nine centers equipped with TB microscopy units were selected to participate in the trial. Among them, fifteen health centers were randomized to the intervention arm (which involves onsite molecular testing using Truenat platform/MTB assays, process process optimization to enable same-day TB diagnosis and treatment initiation, and feedback on Molbio platform performance) or the control arm (which follows routine care, including on-site sputum smear microscopy and the referral of sputum samples to off-site Xpert testing sites). The primary outcome of the study is the absolute number and proportion of participants with TB microbiological confirmation starting TB treatment within 7 days of their first visit. Secondary outcomes include time to bacteriological confirmation, health outcomes up to 60 days from first visit, as well as user preferences, direct cost, and productivity analyses. Ethics and dissemination: TB-CAPT CORE trial has been approved by regulatory and ethical committees in Mozambique and Tanzania, as well as by each partner organization. Consent is informed and voluntary, and confidentiality of participants is maintained throughout. Study findings will be presented at scientific conferences and published in peer-reviewed international journals. Trial Registration: US National Institutes of Health's ClinicalTrials.gov, NCT04568954. Registered 23 September 2020. [ABSTRACT FROM AUTHOR]

Background: Artificial intelligence-based computer-aided detection (AI–CAD) for tuberculosis (TB) has become commercially available and several studies have been conducted to evaluate the performance of AI–CAD for pulmonary tuberculosis (TB) in clinical settings. However, little is known about its applicability to community-based active case-finding (ACF) for TB. Methods: We analysed an anonymized data set obtained from a community-based ACF in Cambodia, targeting persons aged 55 years or over, persons with any TB symptoms, such as chronic cough, and persons at risk of TB, including household contacts. All of the participants in the ACF were screened by chest radiography (CXR) by Cambodian doctors, followed by Xpert test when they were eligible for sputum examination. Interpretation by an experienced chest physician and abnormality scoring by a newly developed AI–CAD were retrospectively conducted for the CXR images. With a reference of Xpert-positive TB or human interpretations, receiver operating characteristic (ROC) curves were drawn to evaluate the AI–CAD performance by area under the ROC curve (AUROC). In addition, its applicability to community-based ACFs in Cambodia was examined. Results: TB scores of the AI–CAD were significantly associated with the CXR classifications as indicated by the severity of TB disease, and its AUROC as the bacteriological reference was 0.86 (95% confidence interval 0.83–0.89). Using a threshold for triage purposes, the human reading and bacteriological examination needed fell to 21% and 15%, respectively, detecting 95% of Xpert-positive TB in ACF. For screening purposes, we could detect 98% of Xpert-positive TB cases. Conclusions: AI–CAD is applicable to community-based ACF in high TB burden settings, where experienced human readers for CXR images are scarce. The use of AI–CAD in developing countries has the potential to expand CXR screening in community-based ACFs, with a substantial decrease in the workload on human readers and laboratory labour. Further studies are needed to generalize the results to other countries by increasing the sample size and comparing the AI–CAD performance with that of more human readers. [ABSTRACT FROM AUTHOR]

Background: This study aims to investigate the outcomes of patients who received early fiberoptic bronchoscopic sputum aspiration and lavage after thoracoscopic and laparoscopic esophagectomy due to esophageal cancer. Methods: A prospective randomized clinical trial was performed between March 2020 and June 2022. Patients who were scheduled for thoracoscopic and laparoscopic esophagectomy due to esophageal cancer were enrolled. Then, these patients were assigned to the control group (traditional postoperative care) and study group (traditional postoperative care with early bronchoscopic sputum aspiration and lavage). The outcomes, which included the length of hospital stay and medical expenses, and postoperative complications, which included pulmonary infection, atelectasis, respiratory dysfunction and anastomotic leakage, were compared between these two groups. Results: A total of 106 patients were enrolled for the present study, and 53 patients were assigned for the control and study groups. There were no statistically significant differences in gender, age, and location of the esophageal cancer between the two groups. Furthermore, the length of hospital stay was statistically significantly shorter and the medical expenses were lower during hospitalization in the study group, when compared to the control group (12.3 ± 1.2 vs. 18.8 ± 1.3 days, 5.5 ± 0.9 vs. 7.2 ± 1.2 Chinese Yuan, respectively; all, P < 0.05). Moreover, there were statistically significantly fewer incidences of overall complications in study group, when compared to the control group (20.7% vs.45.2%, P < 0.05). Conclusions: For patients with esophageal cancer, early fiberoptic bronchoscopic sputum aspiration and lavage after thoracoscopic and laparoscopic esophagectomy can shorten the length of hospital stay, and lower the medical expense and incidence of postoperative complications. [ABSTRACT FROM AUTHOR]

Background: Pulmonary tuberculosis (PTB) diagnosis relies on sputum examination, a challenge in sputum-scarce patients. Alternative non-invasive sampling methods such as face mask sampling (FMS) have been proposed. Objective: To evaluate the value of FMS for PTB diagnosis by assessing its agreement with sputum samples processed by GeneXpert MTB/RIF (Ultra)(Xpert) testing, and describe FMS sensitivity and specificity. Methods: This was a prospective study conducted at the Carrière TB clinic in Guinea. Presumptive TB patients willing to participate were asked to wear a surgical mask containing a polyvinyl alcohol (PVA) strip for thirty minutes. Subsequently, two spot sputum samples were collected, of which one was processed by microscopy on site and the other by Xpert in Guinea's National Reference Laboratory of Mycobacteriology (LNRM). The first 30 FMS were processed at the Supranational Reference Laboratory in Antwerp, Belgium, and the following 118 FMS in the LNRM. Results: One hundred fifty patients participated, of whom 148 had valid results for both mask and sputum. Sputum smear microscopy was positive for 47 (31.8%) patients while sputum-Xpert detected MTB in 54 (36.5%) patients. Among the 54 patients testing sputum-Xpert positive, 26 (48.1%) yielded a positive FMS-Xpert result, while four sputum-Xpert negative patients tested positive for FMS and 90 patients were Xpert-negative for both sputum and mask samples, suggesting a moderate level of agreement (k-value of 0.47). The overall mask sensitivity was 48.1%, with 95.7% specificity. Conclusion: In our setting, Xpert testing on FMS did not yield a high level of agreement to sputum sample. [ABSTRACT FROM AUTHOR]

Background: Smear microscopy has remained the initial diagnostic test for presumptive tuberculosis (TB) patients in health facilities without the World Health Organization (WHO) recommended rapid diagnostic tools. In the Uganda TB laboratory network, the technique remains the only tool to monitor response to treatment among drug susceptible TB patients, with the country currently having over 1,600 microscopy TB testing units. It has been evidenced that acid-fast bacilli (AFB) microscopy's yield highly depends on the staining technique and reading ability of the laboratory personnel. For the quality of TB testing in the country, the TB control program set up a Randomized Blinded Rechecking (RBRC) program in 2008 to monitor the testing performance of laboratories to continuously improve the reliability and efficiency of results. This is the first study to determine the effectiveness and impact of the RBRC program on the performance of the participating laboratories in Uganda. Methods: This was a retrospective cross-sectional study based on a record review of the RBRC's annual results compilations between January 2008 and December 2017. Results: Between January 2008 and December 2017, a total of 265,523 smears were re-checked during the RBRC program. The number of enrolled laboratories in the RBRC program rose from 660 to 2008 to 1,406 in 2017. The RBRC program resulted in a statistically significant reduction in microscopy errors, with false positives decreasing from 12.8% to 2008 to 7.6% in 2017, false positive errors decreasing from 10 to 6.3%, false negative errors decreasing from 2.9 to 0.7%, quantification errors decreasing from 6.0 to 1.8%, and the overall sensitivity of smear microscopy compared to the controllers increased with statistical significance from 93 to 97%. Conclusion: The study reveals an overall significant error reduction and an improved sensitivity of smear microscopy upon continuous implementation of the RBRC program in an AFB microscopy TB laboratory network. Implementation of a RBRC program is crucial and essential to maintaining a reliable TB laboratory service that can facilitate accurate diagnosis and offset the disadvantages of using smear microscopy. [ABSTRACT FROM AUTHOR]

Background: To improve tuberculosis (TB) diagnosis, the World Health Organisation (WHO) has called for a non-sputum based triage test to focus TB testing on people with a high likelihood of having active pulmonary tuberculosis (TB). Various host or pathogen biomarker-based testing devices are in design stage and require validity assessment. Host biomarkers have shown promise to accurately rule out active TB, but further research is required to determine generalisability. The TriageTB diagnostic test study aims to assess the accuracy of diagnostic test candidates, as well as field-test, finalise the design and biomarker signature, and validate a point-of-care multi-biomarker test (MBT). Methods: This observational diagnostic study will evaluate sensitivity and specificity of biomarker-based diagnostic candidates including the MBT and Xpert® TB Fingerstick cartridge compared with a gold-standard composite TB outcome classification defined by symptoms, sputum GeneXpert® Ultra, smear and culture, radiological features, response to TB therapy and presence of an alternative diagnosis. The study will be conducted in research sites in South Africa, Uganda, The Gambia and Vietnam which all have high TB prevalence. The two-phase design allows for finalisation of the MBT in Phase 1 in which candidate host proteins will be evaluated on stored serum from Asia, South Africa and South America and on fingerstick blood from 50 newly recruited participants per site. The MBT test will then be locked down and validated in Phase 2 on 250 participants per site. Discussion: By targeting confirmatory TB testing to those with a positive triage test, 75% of negative GXPU may be avoided, thereby reducing diagnostic costs and patient losses during the care cascade. This study builds on previous biomarker research and aims to identify a point-of-care test meeting or exceeding the minimum World Health Organisation target product profile of a 90% sensitivity and 70% specificity. Streamlining TB testing by identifying individuals with a high likelihood of TB should improve TB resources use and, in so doing, improve TB care. Trial registration: NCT04232618 (clinicaltrials.gov) Date of registration: 16 January 2020. [ABSTRACT FROM AUTHOR]

Background: China is one of 30 countries with a high tuberculosis (TB) burden, and poor adherence to TB treatment is one of the biggest challenges for TB control. We aimed to explore the barriers and facilitators of treatment adherence among drug-sensitive tuberculosis (DS-TB) patients under the "Integrated model" in Western China, to provide evidence-based treatment and control regimens for DS-TB patients to improve adherence behaviours.Methods: Both qualitative and quantitative research methods were used to explore the factors associated with self-reported adherence (SRA) behaviours. Questionnaire surveys with DS-TB patients and in-depth interviews with leaders from the Centers for Disease Control and Prevention (CDC) and community health sectors (CHCs), healthcare workers (HCWs) from CHCs, and DS-TB patients were conducted.Results: A total of 459 eligible patients were included in the quantitative survey, and two patients and 13 healthcare providers were included in the in-depth interviews. The percentage of patients who experienced a missed dose, lack of follow-up sputum examination, and interrupted treatment were 19.0%, 11.3%, and 9.2%, respectively. Patients aged 20-39 had a higher risk of missed dose [OR (95% CI): 2.302 (1.001-5.305)] and a lower risk of interrupted treatment [OR (95% CI): 0.278 (0.077-0.982)] than patients more than 60 years. Patients who were of Han ethnicity (OR [95% CI]: 0.524 [0.301-0.912]) received psychological support (OR [95% CI]: 0.379 [0.144-0.998]) from their family and had a lower risk of missed doses. Patients who had drug side effects had a higher risk of interrupted treatment (OR [95% CI]: 2.587 [1.237-5.412]). Patients who possessed higher knowledge had a lower risk of lack of follow-up sputum examination [OR (95% CI): 0.817 (0.673-0.991)]. The results of the qualitative study also reported that patients' poor TB knowledge was the main reason for their non-SRA behaviours.Conclusions: Patient-centred strategies should be implemented to improve health literacy and strengthen psychological support. More effective case management should be designed and implemented based on different patient characteristics to improve adherence behaviours in further studies. [ABSTRACT FROM AUTHOR]

Background: Chlamydia pneumoniae and Mycoplasma pneumoniae have been implicated in the pathogenesis of asthma and are responsible for chronic inflammation when host immune system fails to eradicate the bacteria.Method: We performed a prospective study on 410 patients who underwent a visit at the asthma clinic of CHU of Liege between June 2016 and June 2018 with serology testing for C. pneumoniae and M. pneumoniae.Results: 65% of our asthmatic population had serum IgA and/or IgG towards C. pneumoniae, while only 12.6% had IgM and/or IgG against M. pneumoniae. Compared to seronegative asthmatics, asthmatics with IgA+ and IgG+ against C. pneumoniae were more often male and older with a higher proportion of patients with smoking history. They received higher doses of inhaled corticosteroids (ICS) and displayed lower FEV1/FVC ratio, higher RV/TLC ratio and lower conductance. They had higher levels of fibrinogen, though in the normal range and had lower sputum eosinophil counts. Patients with IgA- and IgG+ against C. pneumoniae were older and had higher blood monocyte counts and alpha-1-antitrypsin levels as compared to seronegative patients. Patients with IgM and/or IgG towards M. pneumoniae were more often males than seronegative asthmatics. In a subpopulation of 14 neutrophilic asthmatics with Chlamydia pneumoniae IgA + /IgG + treated with macrolides, we found a significant decrease in blood neutrophils and normalization of sputum neutrophil count but no effect on asthma quality of life and exacerbations.Conclusion: Positive Chlamydia serologic test is more common than positive Mycoplasma serology. Asthmatics with IgA and IgG against C. pneumoniae have more severe disease with increased airway obstruction, higher doses of ICS, more signs of air trapping and less type-2 inflammation. [ABSTRACT FROM AUTHOR]

Background: Lung resection in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) has been reported to be associated with favorable outcomes. However, little is known regarding the risk and prognostic factors for refractory and recurrent cases. We aimed to evaluate the overall impact and benefit of adjuvant lung surgery by comparing NTM-PD patients who underwent adjuvant lung resection with those treated exclusively with antibiotics. We also investigated the efficacy of serum IgA antibody against glycopeptidolipid (GPL) core antigen (GPL core antibody) to monitor disease activity and predict the recurrence of disease after adjuvant lung resection.Methods: We retrospectively evaluated the clinical characteristics and surgical outcomes of 35 patients surgically treated for NTM-PD. Furthermore, we compared surgically treated patients and control patients treated exclusively with antibiotics who were matched statistically 1:1 using a propensity score calculated from age, sex, body mass index, and radiologic features of disease.Results: In the surgically treated patients, the median age was 58 (interquartile range, 47-65) years and 65.7% were female. Twenty-eight patients had Mycobacterium avium complex. Operations comprised four pneumonectomies, two bilobectomies, one bilobectomy plus segmentectomy, 17 lobectomies, two segmentectomies, and nine lobectomies plus segmentectomies. Postoperative complications occurred in seven patients (20%), there were no operative deaths, and 33 (94.3%) patients achieved negative sputum culture conversion. Refractory and recurrent cases were associated with remnant bronchiectasis, contralateral shadows, and positive acid-fast bacilli staining or culture. Of 28 statistically matched pairs, long-term sustained negative culture conversion was observed in 23 (82.2%) surgical group patients and in 14 (50.0%) non-surgical group patients (0.0438). The mortality rate was lower in the surgical group, but did not reach statistical significance (one in the surgical group and four in the non-surgical group, p = 0.3516). GPL core antibody was correlated with disease activity and recurrence.Conclusions: NTM-PD patients who underwent adjuvant lung resection experienced overall favorable outcomes and achieved sputum culture conversion more frequently. Long-term mortality may have been reduced by this procedure, and the level of GPL core antibody was shown to be a good clinical indicator of disease activity after surgery. [ABSTRACT FROM AUTHOR]

Background: Delays in diagnosis and treatment of tuberculosis (TB) remain common in high-burden countries. To improve case detection, substantial investments have been made to scale-up Xpert MTB/RIF (Xpert), a cartridge-based nucleic acid amplification test that can detect TB within 2 hours, as a replacement for sputum smear microscopy. However, the optimal strategy for implementation of Xpert testing remains unclear.Methods: The Xpert Performance Evaluation for Linkage to Tuberculosis Care (XPEL-TB) trial uses an ultra-pragmatic, hybrid type II effectiveness-implementation design to assess the effectiveness and implementation of a streamlined strategy for delivery of Xpert testing in real-world settings. Twenty health centers with TB microscopy units were selected to participate in the trial, with ten health centers randomized to the intervention strategy (onsite molecular testing using GeneXpert Edge, process redesign to facilitate same-day TB diagnosis and treatment, and performance feedback) or routine care (onsite sputum smear microscopy plus referral of sputum samples to Xpert testing sites). The primary outcome is the number of patients with microbiologically confirmed TB who were initiated on treatment within 14 days of presentation to the health center, which reflects successful completion of the TB diagnostic evaluation process. Secondary outcomes include health outcomes (6-month vital status), as well as measures of the reach, adoption, and implementation of the intervention strategy.Discussion: The design elements and implementation approach for the XPEL-TB trial were intentionally selected to minimize disruptions to routine care procedures, with the goal of limiting their influence on key primary and secondary outcomes. Trial findings may result in increased support and funding for rapid, onsite molecular testing as the standard-of-care for all patients being evaluated for TB.Trial Registration: US National Institutes of Health's ClinicalTrials.gov, NCT03044158. Registered 06 February 2017. Pan African Clinical Trials Registry, PACTR201610001763265. Registered 03 September 2016. [ABSTRACT FROM AUTHOR]

Background: In-hospital logistic management barriers (LMB) are considered to be important risk factors for delays in TB diagnosis and treatment initiation (TB-dt), which perpetuates TB transmission and the development of TB morbidity and mortality. We assessed the contribution of hospital auxiliary workers (HAWs) and 24-h TB laboratory services using Xpert (24h-Xpert) on the delays in TB-dt and TB mortality at Beira Central Hospital, Mozambique.Methods: A quasi-experimental design was used. Implementation strategy-HAWs and laboratory technicians were selected and trained, accordingly. Interventions-having trained HAW and TB laboratory technicians as expediters of TB LMB issues and assurer of 24h-Xpert, respectively. Implementation outcomes-time from hospital admission to sputum examination results, time from hospital admission to treatment initiation, proportion of same-day TB cases diagnosed, initiated TB treatment, and TB patient with unfavorable outcome after hospitalization (hospital TB mortality). A nonparametric test was used to test the differences between groups and adjusted OR (95% CI) were computed using multivariate logistic regression.Results: We recruited 522 TB patients. Median (IQR) age was 34 (16) years, and 52% were from intervention site, 58% males, 60% new case of TB, 12% MDR-TB, 72% TB/HIV co-infected, and 43% on HIV treatment at admission. In the intervention hospital, 93% of patients had same-day TB-dt in comparison with a median (IQR) time of 15 (2) days in the control hospital. TB mortality in the intervention hospital was lower than that in the control hospital (13% vs 49%). TB patients admitted to the intervention hospital were nine times more likely to obtain an early laboratory diagnosis of TB, six times more likely to reduce delays in TB treatment initiation, and eight times less likely to die, when compared to those who were admitted to the control hospital, adjusting for other factors.Conclusion: In-hospital delays in TB-dt and high TB mortality in Mozambique are common and probably due, in part, to LMB amenable to poor-quality TB care. Task shifting of TB logistic management services to HAWs and lower laboratory technicians, to ensure 24h-Xpert through "on-the-spot strategy," may contribute to timely TB detection, proper treatment, and reduction of TB mortality. [ABSTRACT FROM AUTHOR]

Background: Undiagnosed tuberculosis (TB) remains the most common cause of HIV-related mortality. Xpert MTB/RIF (Xpert) is being rolled out globally to improve TB diagnostic capacity. However, previous Xpert impact trials have reported that health system weaknesses blunted impact of this improved diagnostic tool. During phased Xpert rollout in Botswana, we evaluated the impact of a package of interventions comprising (1) additional support for intensified TB case finding (ICF), (2) active tracing for patients missing clinic appointments to support retention, and (3) Xpert replacing sputum-smear microscopy, on early (6-month) antiretroviral therapy (ART) mortality.Methods: At 22 clinics, ART enrollees > 12 years old were eligible for inclusion in three phases: a retrospective standard of care (SOC), prospective enhanced care (EC), and prospective EC plus Xpert (EC+X) phase. EC and EC+X phases were implemented as a stepped-wedge trial. Participants in the EC phase received SOC plus components 1 (strengthened ICF) and 2 (active tracing) of the intervention package, and participants in the EC+X phase received SOC plus all three intervention package components. Primary and secondary objectives were to compare all-cause 6-month ART mortality between SOC and EC+X and between EC and EC+X phases, respectively. We used adjusted analyses, appropriate for study design, to control for baseline differences in individual-level factors and intra-facility correlation.Results: We enrolled 14,963 eligible patients: 8980 in SOC, 1768 in EC, and 4215 in EC+X phases. Median age of ART enrollees was 35 and 64% were female. Median CD4 cell count was lower in SOC than subsequent phases (184/μL in SOC, 246/μL in EC, and 241/μL in EC+X). By 6 months of ART, 461 (5.3%) of SOC, 54 (3.2%) of EC, and 121 (3.0%) of EC+X enrollees had died. Compared with SOC, 6-month mortality was lower in the EC+X phase (adjusted hazard ratio, 0.77; 95% confidence interval, 0.61-0.97, p = 0.029). Compared with EC enrollees, 6-month mortality was similar among EC+X enrollees.Conclusions: Interventions to strengthen ICF and retention were associated with lower early ART mortality. This new evidence highlights the need to strengthen ICF and retention in many similar settings. Similar to other trials, no additional mortality benefit of replacing sputum-smear microscopy with Xpert was observed.Trial Registration: Retrospectively registered: ClinicalTrials.gov (NCT02538952). [ABSTRACT FROM AUTHOR]

Background: The introduction of Xpert MTB/RIF assay (Xpert) has significantly improved diagnosis of Tuberculosis (TB) in resource limited human immunodeficiency virus (HIV) endemic settings. We aimed to modify the Xpert protocol to improve the detection of Mycobacterium tuberculosis (MTB).Methods: This cross sectional study was conducted among presumptive pulmonary tuberculosis (PTB) patients at Kibong'oto Infectious Diseases Hospital between August and November 2015. Each patient consented to provide 2 samples of raw sputa. One-sputum sample was sedimented using the Petroff's method and divided into two portions. One portion of sediment was inoculated on Lowenstein-Jensen culture media and observed for any growth for up to 8 weeks. Both, raw sputum and the portions of sediments were tested separately using Xpert with a sample reagent ratio of 1:2. Mean age of patients, prevalence of MTB, Xpert sensitivity, specificity, positive and negative predictive value were calculated. An incremental sensitivity was determined. Pearson chi-square and either an independent T or Mann-Whitney U-test were used to compared categorical and continuous variables respectively. A p- value of ≤0.05 was considered significant.Results: Of the 270 presumptive PTB cases, 262 were eligible for analysis. Eight (3%) were excluded due to contaminated culture. Patients' mean age was 42.9 (±SD 15.1) years of which 173 (66%) were female. The overall prevalence of PTB was 112 (43%), of which the Xpert detected 105 (40%) in sediments and 98 (37%) in raw sputa as compared to culture which detected 85 (32%) cases of PTB. Sensitivity, specificity, positive and negative predictive values of Xpert on sputum sediments were 92%, 85%, 74% and 96% respectively. Overall, the incremental sensitivity of Xpert on sediment over raw sputum was 6%. In HIV infected Presumptive PTB, the incremental sensitivity was 12%.Conclusion: Lowering the sample reagent to sediment dilution ratio increases sensitivity of Xpert on MTB detection among presumptive PTB cases, especially in HIV infected individuals. [ABSTRACT FROM AUTHOR]

Background: Up to one third of HIV-infected individuals with suspected TB are sputum-scarce. The Alere Determine™ TB LAM Ag lateral flow strip test can be used to diagnose TB in HIV-infected patients with advanced immunosuppression. However, how urine LAM testing should be incorporated into testing algorithms and in the context of specific patient sub-groups remains unclear.Methods: This study represents a post hoc sub-group analysis of data from a randomized multi-center parent study. The study population consisted of hospitalized HIV-infected patients with suspected TB who were unable to produce sputum and who underwent urine LAM testing. The diagnostic utility of urine LAM for TB in this group was compared to the performance of urine LAM in patients who did produce a sputum sample in the parent study.Results: There were a total of 187 and 2341 patients in the sputum-scarce and sputum-producing cohorts, respectively. 80 of the sputum-scarce patients underwent testing with urine LAM. In comparison to those who did produce sputum, sputum-scarce patients had a younger age, a lower Karnofsky performance score, and a lower weight and BMI at admission. A greater proportion of sputum-scarce patients were urine LAM positive, compared to those who were able to produce sputum (31% vs. 21%, p = 0.04). A higher proportion of sputum-scarce patients died within 8 weeks of admission (32% vs. 24%, p = 0.013). We inferred that 19% of HIV-infected sputum-scarce patients suspected of TB were diagnosed with tuberculosis by urine LAM testing, with an estimated positive predictive value of 63% (95% CI 43-82%).Conclusions: Urine LAM testing can effectively identify tuberculosis in HIV-infected patients who are at a higher risk of mortality yet are unable to generate a sputum sample for diagnostic testing. Our findings support the use of urine LAM testing in sputum-scarce hospitalized HIV-infected patients, and its incorporation into diagnostic algorithms for this patient population. [ABSTRACT FROM AUTHOR]

Background: Maintaining the quality of clinical specimens for tuberculosis (TB) testing is a major challenge in many high TB burden-limited resources countries. Sample referral systems in low and middle income countries are often weak and the maintenance of the cold-chain challenging and very costly for TB programs. The development of transport media allowing the preservation of samples without refrigeration is critical for increasing access to TB diagnostic services and for reducing the costs related to testing.Methods: We evaluated the performance of OMNIgene-SPUTUM (OM-S) reagent for the maintenance of Mycobacterium tuberculosis (MTB) viability in sputum samples in the absence of refrigeration and its capacity to stabilize nucleic acid for molecular testing. A total of 329 sputum specimens from presumptive TB cases collected at the National Reference Laboratory in Tirana, Albania, were either decontaminated by a conventional method or processed with OM-S reagent and stored at room temperature. Samples in OM-S were shipped to the Supranational Reference Laboratory in Milan, Italy, at various times and processed for liquid culture.Results: Our data show that OM-S maintains MTB viability for at least three weeks in the absence of refrigeration and improves the quality of culture resulting in a contamination rate lower than 0.5%. However, a significant delay in the time to culture positivity was observed for samples stored for more than two weeks in OM-S.Conclusions: Overall, OM-S offers multiple benefits both at laboratory and TB national program level by increasing the availability to quality diagnostics, promoting access to health care services and strengthening TB patient care especially in hard to reach populations. [ABSTRACT FROM AUTHOR]

Background: Induced and spontaneous sputum are used to evaluate the airways microbiota. Whether the sputum types can be used interchangeably in microbiota research is unknown. Our aim was to compare microbiota in induced and spontaneous sputum from COPD patients sampled during the same consultation.Methods: COPD patients from Bergen, Norway, were followed between 2006/2010, examined during the stable state and exacerbations. 30 patients delivered 36 sample pairs. DNA was extracted by enzymatic and mechanical lysis methods. The V3-V4 region of the 16S rRNA gene was PCR-amplified and prepared for paired-end sequencing. Illumina Miseq System was used for sequencing, and Quantitative Insights Into Microbial Ecology (QIIME) and Stata were used for bioinformatics and statistical analyses.Results: Approximately 4 million sequences were sorted into 1004 different OTUs and further assigned to 106 different taxa. Pair-wise comparison of both taxonomic composition and beta-diversity revealed significant differences in one or both parameters in 1/3 of sample pairs. Alpha-diversity did not differ. Comparing abundances for each taxa identified, showed statistically significant differences between the mean abundances in induced versus spontaneous samples for 15 taxa when disease state was considered. This included potential pathogens like Haemophilus and Moraxella.Conclusion: When studying microbiota in sputum samples one should take into consideration how samples are collected and avoid the usage of both induced and spontaneous sputum in the same study. [ABSTRACT FROM AUTHOR]

Background: High proportion of TB in people living with HIV (PLHIV) is undiagnosed. Due to this active TB case finding is recommended for HIV clinics in high TB burden countries. Presently sputum examination and chest radiography are frontline tests recommended for HIV infected TB presumptives. Abdominal TB which occurs frequently in PLHIV may be missed even by existing programmatic intensified case finding protocols. This study evaluated the routine use of ultrasonography (USG) for active case finding of abdominal TB in HIV clinics.Methods: Retrospective analysis of eight years' data from an HIV Clinic in a TB hospital in India. Patients underwent chest x-ray, sputum examination, USG abdomen and routine blood tests at entry to HIV care. Case forms were scrutinized for diagnosis of TB, USG findings and CD4 cell counts. Abdominal TB was classified as probable or possible TB. Probable TB was based on presence of two major USG (abdomen) findings suggestive of active TB, or one major USG finding with at least two minor USG findings or at least two symptoms, or any USG finding with microbiologically confirmed active TB at another site. Possible TB was based on the presence of one major USG finding, or the presence of two minor USG findings with at least two symptoms. Bacteriological confirmation was not obtained.Results: Eight hundred and eighty-nine people PLHIV underwent a baseline USG abdomen. One hundred and thirteen of 340 cases already diagnosed with TB and 87 of the 91 newly diagnosed with TB at time of HIV clinic registration had abdominal TB. Non-abdominal symptoms like weight loss, fever and cough were seen in 53% and 22% cases had no symptoms at all. Enlarged abdominal lymph nodes with central caseation, ascitis, splenic microabsesses, bowel thickening and hepatosplenomegaly were the USG findings in these cases.Conclusions: Abdominal TB is a frequent TB site in PLHIV presenting with non-abdominal symptoms. It can be easily detected on basis of features seen on a simple abdominal ultrasound. Abdominal USG should be essential part of intensified TB case finding algorithms for HIV infected people living in high TB burden settings. [ABSTRACT FROM AUTHOR]

Background: Emergence of multidrug- and extensively drug-resistant tuberculosis (M/XDR-TB) is a major hurdle for TB control programs especially in developing countries like China. Resistance to fluoroquinolones is high among MDR-TB patients. Early diagnosis of MDR/pre-XDR-TB is essential for lowering transmission of drug-resistant TB and adjusting the treatment regimen.Methods: Smear-positive sputum specimens (n = 186) were collected from Wuhan Institute for Tuberculosis Control. The DNA was extracted from the specimens and run through a Sanger sequencing assay to detect mutations associated with MDR/pre-XDR-TB including the rpoB core region for rifampicin (RIF) resistance; katG and inhA promoter for isoniazid (INH) resistance; and gyrA for fluoroquinolone (FQ) resistance. Sequencing data were compared to phenotypic Lowenstein-Jensen (L-J) proportion method drug susceptibility testing (DST) results for performance analysis.Results: By comparing the mutation data with phenotypic results, the detection rates of MDR-TB and pre-XDR-TB were 84.31% (43/51) and 83.33% (20/24), respectively. The sequencing assay illustrated good sensitivity for the detection of resistance to RIF (96.92%), INH (86.89%), FQ (77.50%). The specificities of the assay were 98.35% for RIF, 99.20% for INH, and 97.26% for FQ.Conclusions: The sequencing assay is an efficient, accurate method for detection of MDR-TB and pre-XDR-TB from clinical smear-positive sputum specimens, should be considered as a supplemental method for obtaining early DST results before the availability of phenotypic DST results. This could be of benefit to early diagnosis, adjusting the treatment regimen and controlling transmission of drug-resistant TB. [ABSTRACT FROM AUTHOR]

Background: African pouched rats sniffing sputum samples provided by local clinics have significantly increased tuberculosis case findings in Tanzania and Mozambique. The objective of this study was to determine the reproducibility of rat results.Methods: Over an 18-month period 11,869 samples were examined by the rats. Intra-rater reliability was assessed through Yule's Q. Inter-rater reliability was assessed with Krippendorff's alpha.Results: Intra-rater reliability was high, with a mean Yule's Q of 0.9. Inter-rater agreement was fair, with Krippendorf's alpha ranging from 0.15 to 0.45. Both Intra- and Inter-rater reliability was independent of the sex of the animals, but they were positively correlated with age. Both intra- and inter-rater agreement was lowest for samples designated as smear-negative by the clinics.Conclusion: Overall, the reproducibility of tuberculosis detection rat results was fair and diagnostic results were therefore independent of the rats used. [ABSTRACT FROM AUTHOR]

Background: Infective exacerbations of COPD are common and are accompanied by neutrophilic bronchitis in sputum. Increased respiratory iron content has been associated with respiratory tract infection, though it is unclear if this represents a predisposing factor for infection or the sequelae of inflammation. Iron overload, as assessed in the airways, may be an important biomarker for recurrent infective exacerbations of COPD. The purpose of our study was to determine if hemosiderin in sputum macrophages is related to infective exacerbations of COPD.Methods: We undertook a retrospective observational study of 54 consecutive patients who presented with an exacerbation of COPD and had sputum examined including assessment for hemosiderin in alveolar macrophages. The relation between infective exacerbations in the previous two years and the percent of hemosiderin-positive macrophages was analyzed with linear regression. To account for the non-parametric distribution of infective exacerbations, negative binomial regression modelling was used to account for other covariates.Results: The percent of hemosiderin positive alveolar macrophages (hemosiderin index), analyzed parametrically and non-parametrically, demonstrated a significant correlation with increasing numbers of infective exacerbations in the previous two years. In a multivariate regression analysis, hemosiderin index was an independent predictor of infective exacerbations. COPD patients with raised hemosiderin index (≥20%) had higher levels of sputum IL-6 compared to patients with lower levels (<20%).Conclusions: High hemosiderin index in sputum alveolar macrophages measured at the time of AECOPD may be related to the frequency of infective exacerbations of COPD. [ABSTRACT FROM AUTHOR]

Background: International non-governmental organizations (INGOs) have been implementing community-based tuberculosis (TB) care (CBTBC) in Myanmar since 2011. Although the National TB Programme (NTP) ultimately plans to take over CBTBC, there have been no evaluations of the models of care or of the costs of providing CBTBC in Myanmar by INGOs. Methods: This was a descriptive study using routinely-collected programmatic and financial data from four INGOs during 2013 and 2014, adjusted for inflation. Data analysis was performed from the provider perspective. Costs for sputum examination were not included as it was provided free of charge by NTP. We calculated the average cost per year of each programme and cost per patient completing treatment. Results: Four INGOs assisted the NTP by providing CBTBC in areas where access to TB services was challenging. Each INGO faced different issues in their contexts and responded with a diversity of strategies. The total costs ranged from US$ 140 754 to US$ 550 221 during the study period. The cost per patient completing treatment ranged from US$ 215 to US$ 1 076 for new cases and US$ 354 to US$ 1 215 for retreatment cases, depending on the targeted area and the package of services offered. One INGO appeared less costly, more sustainable and patient oriented than others. Conclusions: This study revealed a wide variety of models of care and associated costs for implementing CBTBC in diverse and challenging populations and contexts in Myanmar. Consequently, we recommend a more comprehensive evaluation, including development of a cost model, to estimate the costs of scaling up CBTBC country-wide, and cost-effectiveness studies, to best inform the NTP as it prepares to takeover CBTBC activities from INGOs. While awaiting evidence from these studies, model of CBTBC that have higher sustainability potential and allocate more resources to patient-centered care should be given priority support. [ABSTRACT FROM AUTHOR]

Nearly half of the smear negative pulmonary TB in National TB Programme remain undetected in Haryana (north Indian state), probably due to poor access to chest radiography. A corporate hospital stepped into fill this infrastructure gap in Rewari district of Haryana by sending a mobile van with digital x-ray facilities and paramedic staff. The staff of the public health facility coordinated with the eligible patients and ensured that they visited on the designated day. The District TB Officer interpreted the x-ray and made decisions about diagnosis and treatment. The support was provided between May and Dec 2014 in seven public health centres (primary/secondary level) of the district. A total of 355 patie-nts were examined, of whom 122 (34.4%) were diagnosed as smear negative pulmonary TB and started on treatment according to programme guidelines. This public-private partnership needs to be scaled-up and better designed studies are required to assess community-level impact and cost-effectiveness. [ABSTRACT FROM AUTHOR]

Background: Although the prevalence of tuberculosis has decreased significantly over the past decades, the certain populations with mental illness are at increased risk for tuberculosis infection and transmission. However, no studies have examined the performance of different laboratory examination methods among people with severe mental illness in China.Methods: In this study, we firstly performed a retrospective study to evaluate the feasibility of three routine laboratory methods, including sputum microscopy, solid culture and GeneXpert, to diagnose tuberculosis patients with mental illness.Results: During August 2010 and March 2013, a total of 251 TB patients based on clinical and radiographic criteria with severe mental illness were enrolled in this study. The majority of patients was homeless (97/251, 38.6%), and the other 62 (24.7%) and 92 (36.7%) were from urban and rural region, respectively. The most frequently diagnosed mental illness was schizophrenia, accounting for 84.1% (211/251) of patients available for analysis. In addition, the laboratory received 753 sputum samples collected from these 251 TB patients, of which 76.0% (572/753) of samples were classified as salivary sputum, which were unqualified for microscopy and culture. When the test results were analyzed by patients, the positive numbers of TB patients detected by sputum microscopy, solid culture and GeneXpert were 3 (1.2%), 5 (2.0%) and 5 (2.0%), respectively.Conclusions: In conclusion, our findings reveal that the current laboratory examinations based on sputum samples seem not to be suitable for the diagnosis of active TB in the persons with severe mental illness. The products using a non-invasive specimen such as urine deserve further evaluation, which may generate benefit for the early diagnosis of TB in this special population. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) caused by Mycobacterium tuberculosis is one of the leading causes of death from infectious diseases worldwide. Sputum smear microscopy remains the most widely available pulmonary TB diagnostic tool particularly in resource limited settings. A highly sensitive diagnostic with minimal infrastructure, cost and training is required. Hence, we assessed the diagnostic performance of Loop-mediated isothermal amplification (LAMP) assay in detecting M.tuberculosis infection in sputum sample compared to LED fluorescent smear microscopy and culture.Method: A cross-sectional study was conducted at the University of Gondar Hospital from June 01, 2015 to August 30, 2015. Pulmonary TB diagnosis using sputum LED fluorescence smear microscopy, TB-LAMP assay and culture were done. A descriptive analysis was used to determine demographic characteristics of the study participants. Analysis of sensitivity and specificity for smear microscopy and TB-LAMP compared with culture as a reference test was performed. Cohen's kappa was calculated as a measure of agreement between the tests.Results: A total of 78 pulmonary presumptive TB patients sputum sample were analyzed. The overall sensitivity and specificity of LAMP were 75 and 98%, respectively. Among smear negative sputum samples, 33.3% sensitivity and 100% specificity of LAMP were observed. Smear microscopy showed 78.6% sensitivity and 98% specificity. LAMP and smear in series had sensitivity of 67.8% and specificity of 100%. LAMP and smear in parallel had sensitivity of 85.7% and specificity of 96%. The agreement between LAMP and fluorescent smear microscopy tests was very good (κ = 0.83, P-value ≤0.0001).Conclusions: TB-LAMP showed similar specificity but a slightly lower sensitivity with LED fluorescence microscopy. The specificity of LAMP and smear microscopy in series was high. The sensitivity of LAMP was insufficient for smear negative sputum samples. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) continues to be a major global health problem. While progress has been made to improve TB cure rates, South Africa's 76 % smear-positive pulmonary TB (PTB) case cure rate remains below the WHO target of 85 %. We report on the trends of TB smear non-conversion and their predictors at the end of an intensive phase of treatment, and how this impacted on treatment outcomes of smear-positive PTB cases in Eden District, Western Cape Province, South Africa.Methods: Routinely collected, retrospective data of smear-positive PTB cases from the electronic TB register in Eden District between 2007 and 2013 was extracted. Non-conversion was defined as persistent sputum smear-positive PTB cases at the end of the two or three month intensive phase of treatment. Chi-square test for linear trend and simple linear regression analysis were used to analyse the change in percentages and slope of TB smear non-conversion rates over time. Risk factors for TB non-conversion, and their impact on treatment outcomes, were evaluated using logistic regression models.Results: Of 12,742 total smear-positive PTB cases included in our study, 12.8 % (n = 1627) did not sputum smear convert; 13.3 % (1411 of 10,574) of new cases and 9.9 % (216 of 2168) of re-treatment cases. Although not statistically significant in either new or re-treatment cases, between 2007 and 2013, smear non-conversion decreased from 16.4 to 12.7 % (slope = -0.60; 95 % CI: -1.49 to 0.29; p = 0.142) in new cases, and from 11.3 to 10.8 % in re-treatment cases (slope = -0.29; 95 % CI: -1.06 to 0.48; p = 0.376). Male gender, HIV co-infection and a >2+ acid fast bacilli (AFB) smear grading at the start of TB treatment were independent risk factors for non-conversion (p < 0.001). Age was a risk factor for non-conversion in new cases, but not for re-treatment cases. Non-conversion was also associated with unsuccessful treatment outcomes (p < 0.01), including treatment default and treatment failure.Conclusions: Smear-positive PTB cases, especially men and those with identified risk factors for non-conversion, should be closely monitored throughout their treatment period. The South African TB control program should invest in patient adherence counselling and education to mitigate TB non-conversion risk factors, and to improve conversion and TB cure rates. [ABSTRACT FROM AUTHOR]

Background: Periostin levels are associated with airway eosinophilia and are suppressed by corticosteroid treatment in asthma. This study sought to determine the relationship between serum and sputum periostin, airway inflammatory phenotype and asthma control.Methods: Adults with poorly-controlled asthma (n = 83) underwent a clinical assessment, sputum induction and blood sampling. Dispersed sputum was used for a differential cell count and periostin assessment (ELISA). Serum periostin was determined by the Elecsys® immunoassay.Results: Periostin levels were significantly higher in serum (median (IQR) of 51.6 (41.8, 62.6) ng/mL) than in sputum (1.1 (0.5, 2.0) ng/mL) (p < 0.001). Serum and sputum periostin were significantly higher in patients with eosinophilic asthma (n = 37) compared with non-eosinophilic asthma. Both serum and sputum periostin levels were significantly associated with proportion of sputum eosinophils (r = 0.422, p < 0.001 and r = 0.364, p = 0.005 respectively) but were not associated with asthma control. In receiver operator characteristic curve analysis, the area under the curve (AUC) for serum periostin (n = 83) was 0.679, p = 0.007. Peripheral blood eosinophils assessed in 67 matched samples, had a numerically greater AUC of 0.820 compared with serum periostin, p = 0.086 for the detection of eosinophilic asthma.Conclusion: In poorly-controlled asthma, sputum and serum periostin levels are significantly related to sputum eosinophil proportions while their ability to predict the presence of eosinophilic asthma is modest. [ABSTRACT FROM AUTHOR]

Background: In Zimbabwe, sputum smear microscopy (SSM) is the routinely used TB diagnostic tool in hospitalised HIV-infected patients. However, SSM has poor sensitivity in HIV-infected patients. We compared performance of urine lipoarabinomannan strip test (LAM) and SSM among hospitalized HIV-infected patients with suspected TB.Methods: Hospitalized HIV-infected patients with suspected TB were randomized to LAM plus SSM or SSM alone groups as part of a larger multi-country parent study. Here we present a comparison of LAM versus SSM performance from the Zimbabwe study site. LAM analyses (grade 2 cut-off) were conducted using (i) a microbiological reference standard (MRS; culture positivity for M.tb and designated definite TB) and (ii) a composite reference standard (CRS; definite TB plus probable TB i.e. patients with clinical TB excluded from the culture negative group). CRS constituted the primary analysis.Results: 82/457 (18%) of the patients randomized to the LAM group were M.tuberculosis culture positive. Using CRS, sensitivity (%, 95% CI) of LAM was significantly higher than SSM [49.2 (42.1-56.4) versus 29.4(23.2-36.3); p < 0.001]. Specificity and PPV were 98.1%, and 95.8%, respectively. By contrast, using MRS, LAM sensitivity was similar to SSM and specificity was significantly lower, however, the combined sensitivity of LAM and SSM was significantly higher than that of SSM alone, p = 0.009. Using CRS, LAM sensitivity (%, CI) was CD4 count dependent [60.6(50.7-69.8) at ≤50 cells/μL; 40.0(22.7-59.4) at 51-100 cells/μL, and 32.8(21.0-46.3) at >100 cells/μL. The combined sensitivity of LAM and SSM was higher than SSM alone being highest at CD4 counts <50 cells/μL [67.6(57.9-76.3); p = <0.001]. Specificity of LAM or SSM alone, or of combined LAM and SSM was >97% in all the 3 CD4 strata.Conclusion: Among hospitalized HIV-infected patients with suspected TB, the sensitivity of LAM is significantly higher than that of SSM, especially at low CD4 counts. LAM and SSM are complimentary tests for diagnosis of TB in HIV-infected patients. We recommend a combination of LAM and SSM for TB diagnosis in HIV-infected patients with low CD4 counts in HIV/TB co-endemic countries, where alternative methods are unavailable. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of pulmonary tuberculosis (PTB) and smear-negative pulmonary tuberculosis (SNPT) in resource-limited countries is often solely based on clinical signs, chest X-ray radiography and sputum smear microscopy. We investigated currently used methods for the routine diagnosis of SNPT in the Republic of Congo (RoC) among TB suspected patients. The specific case of HIV positive patients was also studied. Methods: A cross-sectional study was conducted at the anti-tuberculosis center (CAT) of Brazzaville, RoC. Tuberculosis suspects were examined for physical signs of TB. Clinical signs, results from sputum smear microscopy, tuberculin skin test (TST) and chest X-ray were recorded. Results: Of the 772 enrolled participants, 372 were diagnosed PTB. Cough was a common symptom for PTB and no PTB patients. Pale skin, positive TST, weight loss and chest X-ray with abnormalities compatible with PTB (PTB-CXR) were significant indicators of PTB. Thirty-six percent of PTB patients were diagnosed SNPT. This category of patients presented less persistent cough and less PTB-CXR. Anorexia and asthenia were significant indicators of SNPT. In the case of HIV+ patients, 57 % were SNPT with anorexia, asthenia and shorter cough being strong indicators of SNPT. Conclusion: Chest X-ray abnormalities, weight loss, pale skin and positive TST were significant indicators of PTB. Anorexia and asthenia showed good diagnostic performance for SNPT, which deserve to be recommended as index indicators of SNPT diagnosis. Duration of cough is also a relevant indicator, especially for HIV+ patients. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) has remained one of the major public health problems in Zimbabwe with an estimated incidence rate of 552 per 100,000 persons in 2013. The aim of this study was to describe the trends in acid-fast bacilli (AFB) sputum-smear positive (SSP) TB overall and within subpopulations for the period during 2008-2011 in Zimbabwe. Results of this study will contribute towards the evaluation and implementation of targeted TB control interventions. Methods: A cross-sectional study design was used to analyze 40, 110 SSP TB patient records routinely collected during 2008-2011. Incidence trends of SSP TB were described by province, sex, and age group. A Mantel-Haenszel Chi Statistic was calculated to compare each provincial SSP TB notification rate to the national SSP TB notification rate. Results: SSP TB notification rates were higher in the two main urban provinces, the western provinces and Manicaland. The 25-44 year age group accounted for the largest proportion of notified SSP TB. However, the 55-64 year and 65+ age groups had SSP TB notification rates in 2011 higher than the 2008 value. Finally, the average SSP TB notification rate in males was 23 % higher than in females. Conclusion: The findings of this study suggest that TB control has successfully decreased the notification rate of SSP TB in Zimbabwe during 2008-2011. However, the disproportionate distribution of SSP TB among different regions and subpopulations of the country highlights the need for more targeted interventions to accelerate the decline of TB in Zimbabwe. [ABSTRACT FROM AUTHOR]

Background: External quality assessment (EQA) of sputum smear microscopy is essential and indispensable component of any tuberculosis program. This study assessed the EQA of acid fast bacilli (AFB) smear microscopy through onsite evaluation, blinded rechecking and panel test. A one year study was conducted on eight health institution laboratories from December 2011 to December 2012. Onsite evaluation, blinded rechecking and panel tests were used to collect data. Data were analyzed using SPSS version 16. Sensitivity, specificity, predictive values, and proportions of false readings were calculated. The level of agreement was measured using Kappa (?) value. Results: Problems observed during onsite evaluation include shortages of materials, disinfectant, and poor storage and working condition. A total of 578 slides were collected for blinded rechecking, of which 102 (17.6 %) were reported as positive by peripheral laboratories. The panel test revealed an overall error of 17 (25.25 %) of which 14 (17.5 %) were minor errors [low false negative 6 (7.5 %) and low false positive 8 (10 %)], and 3 (3.75 %) were major errors (high false positive). The sensitivity, specificity, positive predictive values (PPV) and negative predictive values (NPV) of the peripheral laboratories were 83.5, 97.8, 91.7, and 95.7, respectively. The false readings at the peripheral laboratories were 32 (5.5 %). Agreement on reading the slides was observed on 546 (94.5 %) slides (K = 0.84, SE = 0.054). Conclusions: Lack of reagents, supplies, favorable working environment and AFB related technical problems were identified in the peripheral laboratories. High false negative error was found to be the predominant major error. A continuous and strong EQA scheme should be implemented to avoid reporting errors and produce quality sputum results. [ABSTRACT FROM AUTHOR]

In 2015, the WHO End TB Strategy laid out ambitious goals to dramatically reduce tuberculosis (TB) deaths, incidence, and catastrophic costs through research, bold new strategies, and patient-centered care. In this commentary, recent evidence on sputum collection strategies for smear microscopy is reviewed, and the argument is made that redesigning smear microscopy as a patient-centered service offers the only realistic and widely available strategy to advance TB diagnostic care towards the initial End TB Strategy goals laid out for 2025. Finally, the successful adoption of same-day sputum smear microscopy as a model for patient-centered TB care is suggested to be synergistic with and to form part of the scale-up of new TB diagnostic tools.Please see related article: https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-017-0947-9. [ABSTRACT FROM AUTHOR]

Background: Culture of Mycobacterium tuberculosis is the gold standard method for the laboratory diagnosis of pulmonary tuberculosis, after effective decontamination. Results: We evaluated squalamine and chlorhexidine to decontaminate sputum specimens for the culture of mycobacteria. Eight sputum specimens were artificially infected with 105 colony-forming units (cfu)/mL Mycobacterium tuberculosis and Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans as contaminants. In the second step, we tested chlorhexidine-based decontamination on 191 clinical specimens, (Chlorhexidine, 0.1, 0.5 and 0.7 %). In a last step, growth of contaminants and mycobacteria was measured in 75 consecutive sputum specimens using the routine NALC-NaOH decontamination protocol or with 0.7 % chlorhexidine decontamination and an inoculation on Coletsos medium. In the artificially model, contaminants grew in 100 % of the artificially infected sputum specimens decontaminated using 100 mg/mL squalamine, in 62.5 % of specimens decontaminated using N-Acetyl-L-Cysteine-Sodium Hydroxide (NALC-NaOH), and in 0 % of specimens decontaminated using 0.1 %, 0.35 %, or 1 % chlorhexidine (P < 0.05). These specimens yielded <102 cfu M. tuberculosis using NALC-NaOH and > 1.4.102 cfu M. tuberculosis when any concentration of chlorhexidine was used (P < 0.05). In the second step we found that 0.7 %-chlorhexidine yielded 0 % contamination rate, 3.2 % for 0.5 %-chlorhexidine and 28.3 % for 0.1 %-chlorhexidine. As for the 75 specimens treated in parallel by both methods we found that when using the standard NALC-NaOH decontamination method, 8/75 (10.7 %) specimens yielded M. tuberculosis colonies with a time to detection of 17.5 ± 3 days and an 8 % contamination rate. Additionally, 14 specimens yielded mycobacteria colonies (12 M. tuberculosis, and 2 Mycobacterium bolletii) (18.7 %) (P = 0.25), which has yielded a 100 % sensitivity for the chlorhexidine protocol. Time to detection was of 15.86 ± 4.7 days (P = 0.39) and a 0 % contamination rate (P < 0.05) using the 0.7 %-chlorhexidine protocol. Conclusion: In our work we showed for the first time that chlorhexidine based decontamination is superior to the standard NALC-NaOH method in the isolation of M. tuberculosis from sputum specimens. We currently use 0.7 %-chlorhexidine for the routine decontamination of sputum specimens for the isolation of M. tuberculosis and non-tuberculosis mycobacteria on egg-lecithin containing media. [ABSTRACT FROM AUTHOR]

Background: In limited resource settings, sputum smear conversion at the end of the intensive phase of tuberculosis treatment is an indicator not only of patients' response to treatment, but also of anti-tuberculosis program performance. The objective of this study was to identify factors associated to sputum smear non-conversion at the end of the intensive phase of treatment, and the effect of smear non-conversion on the outcome of smear-positive pulmonary tuberculosis patients. Method: This retrospective cohort study was carried out on data of patients treated in the Diagnostic and Treatment Centre of Baleng, West-Cameroon from 2006 to 2012. Logistic regression models were used to evaluate the association of socio-demographic and clinical factors with delay in sputum smear conversion, and the association of this delay with treatment outcomes. Result: Out of 1425 smear-positive pulmonary tuberculosis patients treated during the study period, 1286 (90.2%) were included in the analysis. Ninety four (7.3% CI: 6.0- 8.9) patients were identified as non-converted at the end of the intensive phase of treatment. Pre-treatment smears graded 2+ and 3+ were independently associated to delay in smear conversion (p < 0.01). Years of treatment ranging from 2009 to 2012 were also associated to delay in smear conversion (p < 0.02). Delay in smear conversion was significantly associated to failure [Adjusted Odd Ratio (AOR):12.4 (Confidence Interval: CI 4.0- 39.0)] and death, AOR: 3.6 (CI 1.5- 9.0). Conclusion: Heavy initial bacillary load and treatment years ranging from 2009 to2012 were associated to sputum smear non-conversion at the end of the intensive phase of TB treatment. Also, delay in smear conversion was associated to unfavorable treatment outcomes. Patients with heavy initial bacillary load should thus be closely monitored and studies done to identify reasons for the high proportion of non-conversion among patients treated between 2009 and 2012. [ABSTRACT FROM AUTHOR]

Background: The GeneXpertMTB/RIF (Xpert) assay is now recommended by WHO for diagnosis of tuberculosis (TB) in children but evaluation data is limited. Methods: One hundred and fifty consecutive HIV negative children (<15 years of age) presenting with suspected TB were enrolled at a TB referral hospital in Ho Chi Minh City, Vietnam. 302 samples including sputum (n = 79), gastric fluid (n = 215), CSF (n = 3), pleural fluid (n = 4) and cervical lymphadenopathic pus (n = 1) were tested by smear, automated liquid culture (Bactec MGIT) and Xpert. Patients were classified retrospectively using the standardised case definition into confirmed, probable, possible, TB unlikely or not TB categories. Test accuracy was evaluated against 2 gold standards: [1] clinical (confirmed, probable and possible TB) and [2] 'confirmed TB' alone. Results: The median age of participants was 18 months [IQR 5-170]. When test results were aggregated by patient, the sensitivity of smear, Xpert and MGIT against clinical diagnosis as the gold standard were 9.2% (n = 12/131) [95%CI 4.2; 14.1], 20.6% (n = 27/131) [95%CI 13.7; 27.5] and 29.0% (n = 38/131) [21.2;36.8], respectively. Specificity 100% (n = 19/19), 94.7% (n = 18/19), 94.7% (n = 18/19), respectively. Xpert was more sensitive than smear (P = <0.001) and less sensitive than MGIT (P = 0.002). Conclusions: The systematic use of Xpert will increase early TB case confirmation in children and represents a major advance but sensitivity of all tests remains unacceptably low. Improved rapid diagnostic tests and algorithm approaches for pediatric TB are still an urgent research priority. [ABSTRACT FROM AUTHOR]

Background The Global Initiative defines COPD for chronic obstructive lung disease as an entirely preventable and treatable disease characterized by sputum production, bacterial colonisation, neutrophilic bronchial airway inflammation and poor health status. The World Health Organization (WHO) estimates that COPD will become the fourth-most common cause of death worldwide, just behind ischemic heart disease, cerebrovascular disease and HIV/AIDS, by 2030. The aim of this study was to determine the main structure feature of sputum potentially pathogenic microorganisms in subjects with COPD during the clinical stable state. Methods We employed a molecular genetics-based investigation of the bacteria community, including DNA isolation, PCR amplification and DGGE profiling. PCR-denaturing gradient gel electrophoresis (DGGE) with universal primers targeting the V3 region of the 16S rRNA gene was employed to characterize the overall COPD patient sputum microbiota composition, and some excised gel bands were cloned for sequencing. Real-time PCR was further utilized to quantitatively analyze the subpopulation of microbiota using group-specific primers targeting Streptococcus pneumoniae, Klebsiella pneumoniae, Pseudomonas aeruginosa. Results The DGGE profiles of two groups displayed significant differences between COPD and healthy groups (P < 0.05). Real-time PCR revealed significant increases of Streptococcus pneumoniae, Klebsiella pneumoniae and Pseudomonas aeruginosa (P < 0.05) in the COPD group compared with the healthy group. Conclusion This study revealed strong relationship between alterations of sputum microbiota and COPD. By determining the content of several types of bacteria, we can provide evidence to aid in the diagnosis and treatment of COPD. [ABSTRACT FROM AUTHOR]

Background: Studies from both developed and developing countries have demonstrated a considerable fluctuation in the average cost of TB treatment. The objective of this study was to analyze the medical resource utilization among new smear positive pulmonary tuberculosis patients. We also estimated the cost of tuberculosis treatment from the provider and patient perspectives, and identified the significant cost driving factors. Methods: All new smear positive pulmonary tuberculosis patients who were registered at the chest clinic of the Penang General Hospital, between March 2010 and February 2011, were invited to participate in the study. Provider sector costs were estimated using bottom-up, micro-costing technique. For the calculation of costs from the patients' perspective, all eligible patients who agreed to participate in the study were interviewed after the intensive phase and subsequently at the end of the treatment by a trained nurse. PASW was used to analyze the data (Predictive Analysis SoftWare, version 19.0, Armonk, NY: IBM Corp.). Results: During the study period, 226 patients completed the treatment. However, complete costing data were available for 212 patients. The most highly utilized resources were chest X-ray followed by sputum smear examination. Only a smaller proportion of the patients were hospitalized. The average provider sector cost was MYR 992.34 (i.e., USD 325.35 per patient) whereby the average patient sector cost was MYR 1225.80 (i.e., USD 401.90 per patient). The average patient sector cost of our study population accounted for 5.7% of their annual family income. In multiple linear regression analysis, prolonged treatment duration (i.e., > 6 months) was the only predictor of higher provider sector costs whereby higher patient sector costs were determined by greater household income and persistent cough at the end of the intensive phase of the treatment. Conclusion: In relation to average provider sector cost, our estimates are substantially higher than the budget allocated by the Ministry of Health for the treatment of a tuberculosis case in Malaysia. The expenses borne by the patients and their families on the treatment of the current episode of tuberculosis were not catastrophic for them. [ABSTRACT FROM AUTHOR]

Background Using the Directly Observed Treatment-Short course (DOTS) program the World Health Organization's global target was to detect 70% of new sputum-smear positive PTB cases. Smear positive PTB cases are more infectious than the smear negative cases. The TB case detection rate remains very low in Ethiopia, but there are increases in smear-negative PTB diagnosis which could be attributed to several factors including poor quality of sputum smear-microscopy. Methods A five years retrospective record review of data between September, 2007 and August, 2012 and an in-depth assessment of AFB staining practices of sputum smear using a standard checklist were made. The proportion of smear positive cases relative to overall Acid Fast Bacilli (AFB) screened was determined over a five year period to indicate the overall prevalence and the trend. Odds ratio with 95 percent confidence interval was calculated for categorical variables using multivariate Logistic Regression model to assess the strength of association. Result A total of 1266 individuals' data were reviewed. The majority of the study participants were male, 704 (55.6%), and rural residents, 690 (54.5%). The overall prevalence rate of smear positive PTB was 21.6%. Age categories between 15-24 and 25-34 years were independent predictors of smear positive PTB with adjusted odds ratio of 2.246 [95% CI (1.098-4.597)] and 2.267 [95% CI (1.107-4.642)], respectively. More males were affected by PTB than females with an adjusted odds ratio of 1.426 [95% CI (1.083-1.879)]. An in-depth interview with the respective laboratory chiefs showed that quality control measures for sputum smear microscopy were used at different levels of the testing activities; however, equipment function verification as a quality control measure was not accomplished regularly in all of the study hospital laboratories. Conclusion The smear positive PTB case detection rate indicated in this study is significantly lower than the countries which met the 70% target of the World Health Organization. Lack of feedback mechanisms in the External Quality Assurance schemes of sputum smear microscopy render the opportunity for improvement difficult; Serial sputum examination showed a considerable rate of positivity in the second sputum sample when compared with the others. [ABSTRACT FROM AUTHOR]

Background The aim of this study was to test whether repeatable biomarkers collected from serum, bronchoalveolar lavage (BAL) and sputum of healthy smokers and smokers with COPD would have a prognostic value with respect to the decline in lung function over a 5 year period. Methods In 2006/2007 we had repeatedly collected serum, BAL and sputum of 23 healthy smokers and 24 smokers with COPD (GOLD II) and analysed a panel of more than 100 different parameters. In 2012 we reinvited these subjects to assess the change in lung function to enable the investigation of the potential prognostic value of the 2006/2007 markers and to determine the long-term repeatability of selected blood and serum markers. In this follow-up study we performed body-plethysmography, a blood gas analysis and collected blood and urine samples. The change in lung function was compared with 67 markers from BAL, sputum, serum and whole blood that were shown in the 2006/2007 assessment to be repeatable over a 6 week period. Results We were able to recruit 13 (54%) smokers with COPD and 11 (48%) former healthy smokers that participated in the 2006/2007 study. The decline in lung function was larger in COPD smokers; five of them changed to GOLD III, one to GOLD IV. Two healthy smokers changed to GOLD I. Blood cells, serum von Willebrand factor and alpha-1-antitrypsin showed a good repeatability over 5 years. In COPD smokers a weak correlation between 2006/2007 sputum markers of neutrophilic inflammation and the 5 year change in FEV1/FVC was found. Conclusions Our data suggests that inter-individual and group differences are maintained over a five year period. Despite the large panel of markers available for this analysis, a potential prognostic value appears to exist only for some sputum inflammatory markers. If these data can be confirmed in larger COPD cohorts, it would emphasize the value of sputum markers in clinical trials and support the assumption that an anti-inflammatory treatment can have long term benefits in COPD. [ABSTRACT FROM AUTHOR]

Background This paper reports findings from the prevalence survey conducted in Shandong China in 2010, a province with a population of 94 million. This study aimed to estimate TB prevalence of the province in 2010 in comparison with the 2000 survey; and to compare yields of TB cases from different case finding approaches. Methods A population based, cross-sectional survey was conducted using multi-stage random cluster sampling. 54,279 adults participated in the survey with a response rate of 96%. Doctors interviewed and classified participants as suspected TB cases if they presented with persistent cough, abnormal chest X-ray (CXRAY), or both. Three sputum specimens of all suspected cases were collected and sent for smear microscopy and culture. Results Adjusted prevalence rate of bacteriologically confirmed cases was 34 per 100,000 for adults in Shandong in 2010. Compared to the 2000 survey, TB prevalence has declined by 80%. 53% of bacteriologically confirmed cases did not present persistent cough. The yield of bacteriologically confirmed cases was 47% by symptom screening and 95% by CXRAY. Over 50% of TB cases were among over 65's. Conclusions The prevalence rate of bacteriologically confirmed cases was significantly reduced compared with 2000. The survey raised challenges to identify TB cases without clear symptoms. [ABSTRACT FROM AUTHOR]

Background The acute inhalation of endotoxin mimicks several aspects of the inflammation related to chronic obstructive pulmonary disease (COPD). The aim of the current study was to identify and to validate biomarkers of endotoxin-induced airways' inflammation. Methods The cellular count in the induced-sputum, was measured before and after an inhalation of 20 mcg endotoxin, in 8 healthy volunteers. A proteomic analysis was applied to identify the more relevant proteins expression, before measurement by ELISA. The amplitude and the repeatability of the markers were evaluated among another population of 12 healthy subjects. Results There was a significant rise of viable cells (p <0.01), macrophages (p <0.05), and neutrophils (p <0.02) 24 hours after endotoxin inhalation, and of neutrophils (p <0.02) and lymphocytes (p <0.05) at 6 hours. Among the highest amplitude responses, the two dimensional electrophoretic separation shown proteolytic activity and overexpression of protein spots. By MALDI-TOF mass spectrometry, the last were identified as calgranulin A and B. The expression of the bioactive A/B heterodimeric complex was confirmed by ELISA both in the sputum (p <0.01) and at the blood level (p <0.01). The intra-subject repeatability of the sputum calgranulin A/B was highly significant (p <0.0001). Conclusion In healthy subjects, the inhalation of endotoxin induced expression of sputum calgranulin A/B that could be a biomarker of the endotoxin response/exposure. [ABSTRACT FROM AUTHOR]

Background Reducing mortality from HIV-associated tuberculosis (TB) requires diagnostic tools that are rapid and have high sensitivity among patients with poor prognosis. We determined the relationship between disease severity and the sensitivity of new sputum-based and urine-based diagnostic assays. Methods Consecutive ambulatory patients enrolling for antiretroviral treatment in South Africa were screened for TB regardless of symptoms using diagnostic assays prospectively applied to sputum (fluorescence smear microscopy, Xpert MTB/RIF and liquid culture (reference standard)) and retrospectively applied to stored urine samples (Determine TB-LAM and Xpert MTB/RIF). Assay sensitivities were calculated stratified according to pre-defined indices of disease severity: CD4 count, symptom intensity, serum C-reactive protein (CRP), hemoglobin concentration and vital status at 90 days. Results Sputum culture-positive TB was diagnosed in 15% (89/602) of patients screened and data from 86 patients were analyzed (median CD4 count, 131 cells/µL) including 6 (7%) who died. The sensitivity of sputum microscopy was 26.7% overall and varied relatively little with disease severity. In marked contrast, the sensitivities of urine-based and sputum-based diagnosis using Determine TB-LAM and Xpert MTB/RIF assays were substantially greater in sub-groups with poorer prognosis. Rapid diagnosis from sputum and/or urine samples was possible in >80% of patients in sub-groups with poor prognosis as defined by either CD4 counts <100 cells/µL, advanced symptoms, CRP concentrations >200 mg/L or hemoglobin <8.0 g/dl. Retrospective testing of urine samples with Determine TB-LAM correctly identified all those with TB who died. Conclusions The sensitivities of Xpert MTB/RIF and Determine TB-LAM for HIV-associated TB were highest among HIV-infected patients with the most advanced disease and poorest prognostic characteristics. These data provide strong justification for large-scale intervention studies that assess the impact on survival of screening using these new sputum-based and urine-based diagnostic approaches. [ABSTRACT FROM AUTHOR]

Background: Bacteriological examination of sputum is the cornerstone in diagnosis of pulmonary tuberculosis in developing world, which is usually done using a Ziehl-Nelseen (ZN) method. However, due to limited laboratory facilities that can satisfy the procedure, applicability of this procedure appears to be adversely affected in field conditions and at peripheral health institutions. Hence, it has become necessary to look for a procedure which can be used as alternative in such conditions. In a cross-sectional study, using convenient sampling technique 362 pulmonary tuberculosis suspected patients who attended at Mekelle University Hospital (MUH) between November 2011 and February 2012 were included. After obtaining an informed consent, spot- morning-spot sputum samples were collected from suspected patients. Then a set of duplicate slides, of which one was allocated to a two-reagent cold method (a method of staining which requires carbol fuchsine as a primary stain and Gabbet's methylene blue both as a decolorizer and counter stain) and the other to the Zeihl-Nelseen method were smeared evenly from representative portion of each specimen using the protocol for duplicate smear preparation. Stained smears were read blindly by two technologists at different occasions. Finally to assure quality, all positive smears and 25% of the negative smears were cross checked by senior experienced examiner. Findings: Overall concordance between the two methods was 99.7% (kappa (κ) = 0.98; 95%, confidence interval 0.93-1.00), and the observed agreement was statistically significant (p<0.001). When evaluated against Ziehl-Nelseen method, sensitivity and specificity of the two-reagent cold staining method were 95.8% (95% confidence interval 93.7-97.9) and 100% respectively. Positive and negative predictive values of the two-reagent cold staining method were respectively 100% and 99.7%. Positive and negative agreements between the two techniques were respectively 97.9% and 99.9%. Conclusion: The two-reagent cold staining method was found to be a suitable alternative to the conventional Ziehl-Nelseen method; it was at least as specific as Ziehl-Neelsen method although somewhat less sensitive. However, large scale multicentric studies need to be performed for further evaluation of this cold staining method. [ABSTRACT FROM AUTHOR]

Background: It has been suggested that smoking asthmatics benefit less from corticosteroid treatment than neversmoking asthmatics. We investigated differences in blood and sputum inflammatory profiles between ex-, current-, and never-smokers and assessed their ICS treatment response after 2-week and 1-year treatment. Methods: We analyzed FEV1, PC20 methacholine and PC20 AMP, (differential) cell counts in sputum and blood in ex-, current- and never-smokers at baseline (n=114), after 2-week treatment with fluticasone 500 or 2000 μg/day (n=76) and after 1-year treatment with fluticasone 500 μg/day or a variable dose of fluticasone based on a selfmanagement plan (n=64). Results: A total of 114 patients were included (29 ex-, 30 current- and 55 never-smokers. At baseline, ex- and current-smokers had less eosinophils in sputum and blood than never-smokers. Blood neutrophil counts were higher in current- than in never-smokers. A higher number of cigarettes smoked daily was associated with lower blood and sputum eosinophils. After 2-week ICS treatment, FEV1 %predicted improved less in current-smokers than never-smokers (2.4% versus 8.1%, p=0.010) and ex-smokers tended to improve less than never-smokers (4.1%, p=0.067). In contrast, no differences in ICS treatment response in lung function or inflammatory cells were found between the three groups after 1 year. Conclusions: Ex- and current-smokers have less eosinophils and more neutrophils in their sputum and blood than never-smokers. Although ex- and current-smokers have a reduced short-term corticosteroid treatment response, we did not find a difference in their long-term treatment response. [ABSTRACT FROM AUTHOR]

Background: Spontaneous regression of lesions occurs in non-infectious benign diseases, such as sarcoidosis, as well as in infectious diseases, such as tuberculosis. Lung cancer and malignant lymphoma, on the other hand, rarely follow a similar course. We report a rare case of lung tuberculosis that presented with multiple nodules with metachronous changes in size. Case presentation: We describe the case of a 50-year-old immunocompetent Japanese man with pulmonary tuberculosis in the form of multifocal nodules. He came to our hospital because of a chest X-ray abnormality. During the course of observation, some nodules reduced while others enlarged in size. Two years after the first visit, fever and pleural effusion appeared. The sputum examination turned out to be positive for tuberculosis. A course of anti-tubercular agents resolved the pleural effusion and multifocal nodules. Conclusion: Differences in the manner of granuloma formation suggest that the local immune response can be different even in the same lung field [ABSTRACT FROM AUTHOR]

Background: Sputum smear microscopy is fast and inexpensive technique for detecting tuberculosis (TB) in high incidence areas but has low sensitivity. Physical and chemical sputum processing along with centrifugation have been found to show promise in overcoming this limitation. Our objective was to compare the sensitivity of smear microscopy obtained with smears made directly from respiratory specimens to those from concentrated specimens. Methods: By active screening, 915 TB suspects were identified from Dhaka Central Jail and sputum specimens were aseptically collected. Direct smears were prepared by taking a small portion of the purulent part of the sputum with a sterile loop. The specimens were then processed by a standard N-acetyl-L-cysteine-NaOH digestion-decontamination method to prepare concentrated specimens. Both smears were then air dried, heat fixed, and stained by the Ziehl-Neelsen staining technique. The stained slides were examined under oil immersion and were graded following International Union Against Tuberculosis and Lung Diseases guidelines. All the specimens were inoculated into Lowenstein-Jensen (L-J) media and culture results were considered as gold standard to calculate sensitivity. Results: Of 915 specimens, 73 (8%) specimens were positive both on direct and concentrated methods, one sample was positive on direct microscopy but was negative on concentrated method. An extra 14 (1.5%) samples were positive on concentrated method which were negative on direct smear. In L-J media 105 specimens were found positive for TB bacilli and of them, 74 (70.5%) and 87 (82.9%) were positive in direct and concentrated smear, respectively. The sensitivity of direct and concentrated smear microscopy was different when using positive culture as the gold standard (71% vs. 83%). Conclusions: The results showed that concentrated technique increases the sensitivity of microscopy up to 12%. Therefore, the national programs in high TB burden countries may consider incorporating the technique into their guidelines at least in the district and higher level laboratories to improve case finding strategy. [ABSTRACT FROM AUTHOR]

Background: There is emerging evidence for the presence of an extensive microbiota in human lungs. It is not known whether variations in the prevalence of species of microbiota in the lungs may have aetiological significance in respiratory conditions such as asthma. The aim of the study was to undertake semi-quantitative analysis of the differences in fungal species in pooled sputum samples from asthma patients and controls. Methods: Induced sputum samples were collected in a case control study of asthma patients and control subjects drawn from the community in Wandsworth, London. Samples from both groups were pooled and then tested for eukaryotes. DNA was amplified using standard PCR techniques, followed by pyrosequencing and comparison of reads to databases of known sequences to determine in a semi-quantitative way the percentage of DNA from known species in each of the two pooled samples. Results: A total of 136 fungal species were identified in the induced sputum samples, with 90 species more common in asthma patients and 46 species more common in control subjects. Psathyrella candolleana, Malassezia pachydermatis, Termitomyces clypeatus and Grifola sordulenta showed a higher percentage of reads in the sputum of asthma patients and Eremothecium sinecaudum, Systenostrema alba, Cladosporium cladosporioides and Vanderwaltozyma polyspora showed a higher percentage of reads in the sputum of control subjects. A statistically significant difference in the pattern of fungi that were present in the respective samples was demonstrated using the Phylogenetic (P) test (P < 0.0001). Conclusion: This study is novel in providing evidence for the widespread nature of fungi in the sputum of healthy and asthmatic individuals. Differences in the pattern of fungi present in asthma patients and controls merit further investigation. Of particular interest was the presence of Malassezia pachydermatis, which is known to be associated with atopic dermatitis. [ABSTRACT FROM AUTHOR]

A 75-year-old man complained of sputum and was referred to our department. His sputum cytology was class III. Chest X-ray and computed tomography showed no abnormalities, but bronchoscopy revealed an elevated lesion in the membranous portion of the left main bronchus, which was pathologically diagnosed as squamous cell carcinoma in situ. Since bronchoscopy revealed no other lesions in the visible parts of the airway, it was considered to be a solitary, early lung cancer, and sleeve resection of the left main bronchus was performed. The postoperative pathological diagnosis was squamous cell carcinoma in situ, pTisN0M0, stage 0. In recent years, an increasing number of studies have reported photodynamic therapy and brachytherapy for the treatment of early lung cancer. However, aggressive bronchoplastic surgery with emphasis on curability should be considered for lesions that are deemed resectable based on their number and extent of invasion. [ABSTRACT FROM AUTHOR]