Despite recent advances in diagnosis, tuberculosis (TB) remains one of the ten leading causes of death worldwide. Here, we engineered Mycobacterium tuberculosis (Mtb) proteins (ESAT6, CFP10, and MTB7.7) to self-assemble into core-shell nanobeads for enhanced TB diagnosis. Respective purified Mtb antigen-coated polyester beads were characterized and their functionality in TB diagnosis was tested in whole blood cytokine release assays. Sensitivity and specificity were studied in 11 pulmonary TB patients (PTB) and 26 healthy individuals composed of 14 Tuberculin Skin Test negative (TSTn) and 12 TST positive (TSTp). The production of 6 cytokines was determined (IFNγ, IP10, IL2, TNFα, CCL3, and CCL11). To differentiate PTB from healthy individuals (TSTp + TSTn), the best individual cytokines were IL2 and CCL11 (>80% sensitivity and specificity) and the best combination was IP10 + IL2 (>90% sensitivity and specificity). We describe an innovative approach using full-length antigens attached to biopolyester nanobeads enabling sensitive and specific detection of human TB.
Smear-positive pulmonary tuberculosis (PTB) is more infectious compared to smear-negative PTB and have great significance for epidemiology and infection control. The prevalence of smear-positive PTB rarely affects males and females equally. Hence, we aimed to identify the sex-related differences in the prevalence of smear-positive PTB and its associated factors in Kuala Lumpur, Malaysia. A cross-sectional study was conducted using data from the National Tuberculosis Information System (TBIS) from 1 January, 2015, to 31 December, 2019. The study population was selected using simple random sampling from the list of registered PTB patients in TBIS. The criteria for inclusion were all Malaysian adults aged ≥18 years residing in Kuala Lumpur and registered as PTB in TBIS. Factors associated with smear-positive PTB in male and female patients were determined using multiple logistic regression analysis. Overall prevalence of smear-positive PTB was 68.6%, and male patients predominated (71%). The male:female prevalence ratio of smear-positive PTB was 2.4:1. Male patients who worked as machine operators and elementary workers (adjusted odds ratio (aOR) 2.23, 95% confidence interval (CI) 1.24-4.02, p = 0.007), were self-employed (aOR 2.58, 95% CI 1.46-4.56, p = 0.001), lived in a residence categorized as 'other' (aOR 2.49, 95% CI 1.28-4.86, p = 0.007) and were smokers (aOR 1.37, 95% CI 1.01-1.87, p = 0.045) had higher odds for smear-positive PTB. Meanwhile, female patients with diabetes mellitus had higher odds for smear-positive PTB (aOR 1.92, 95% CI 1.05-3.54, p = 0.035), while female patients who were healthcare workers had lower odds (aOR 0.33, 95% CI 0.12, 0.94, p = 0.039). The prevalence of smear-positive PTB is higher in males compared to females. The factors associated with smear-positive PTB differed based on sex. The current TB control program, especially on smear-positive PTB, should likely be strategized and stratified by sex.
Pneumocystis pneumonia (PCP) and pulmonary tuberculosis infection (PTB) are important opportunistic infections in HIV-infected patients. The diagnosis remains challenging since Pneumocystis jirovecii cannot be cultured, and expectorated-sputum is frequently difficult to obtain. The monoclonal-antibody detection for P. jirovecii from induced sputum is promising in diagnosing PCP. This study determined the percentage of PCP in HIV-infected patients with pulmonary infiltrates at three government hospitals in Jakarta. The concurrent infection of PTB was carefully documented as well. This cross-sectional study was carried out by documenting the clinical symptoms, laboratory findings, chest X-ray, while clinical outcomes were evaluated during hospitalization. The sputum induction was conducted for P. jirovecii with monoclonal antibody detection at the laboratory of Parasitology Department, Faculty of Medicine Universitas Indonesia, as well as Ziehl-Nielsen staining for PTB. The results indicated that of 55 HIV-infected patients with pulmonary infiltrates, the positive monoclonal antibody for P. jirovecii was detected in eight patients (14.6%). Weight loss, fever, shortness of breath, and crackles were found in all PCP patients; while dry cough in five patients. Moreover, PTB cases with positive acid-fast bacilli (AFB) was detected in five patients (9.1%), the PTB cases with negative AFB was 43.6% (24 out of 55 patients), and the rest 26 patients (47.3%) were not proven to have PTB. The concurrent infections of PCP and PTB were documented in three out of five positive AFB patients. The clinical outcome of eight PCP patients showed improvement in five patients, but the other three patients died. Laboratory findings play an important role in the diagnosis of PCP and PTB, along with clinical characteristics and radiological features. Low CD4+ cell count was considered a possible risk factor for PCP and poor clinical outcomes.
The purpose of this study was to investigate the composition of throat microbiota in pulmonary tuberculosis patients (PTB) in comparison to healthy tuberculin skin test positive (TSTp) and negative (TSTn) individuals. Throat swabs samples were collected, and the microbiota was characterized. Richer operational taxonomic units (OTUs) were present in PTB group, compared to TSTp and TSTn. Regarding alpha diversity analysis there was a higher community diversity in TSTn compared to TSTp. Beta diversity analysis showed different species composition in TSTp compared to TSTn and PTB. There was higher presence of Firmicutes in PTB and TSTn compared to TSTp group at phylum level. At the genus level, Leuconostoc and Enterococcus were higher in TSTn compared to TSTp and Pediococcus, Chryseobacterium, Bifidobacterium, Butyrivibrio, and Bulleidia were higher in PTB compared to TSTn. Streptococcus was higher in TSTn compared to PTB and Lactobacillus in PTB compared to TSTp. At species level, Streptococcus sobrinus and Bulleidia moorei were higher in PTB compared to TSTn individuals, while Lactobacillus salivarius was higher in PTB compared to TSTp. The differences in the microbiome composition could influence the resistance/susceptibility to Mtb infection.
Tuberculosis is a nimble chameleon. It can manifest itself in various ways with atypical clinical and radiographic findings. In this report we discuss the importance of radiographic findings (nodular or mass-like forms) requiring a correlation with microbiological and histopathological results to differentiate lung cancer from TB.
Leprosy and tuberculosis (TB) are endemic to India, however, their coinfection is not frequently encountered in clinical practice. Here, we report a 32-year-old female patient who presented with a history of high-grade intermittent fever, cough and painless skin lesions since a month, along with bilateral claw hand (on examination). The haematological profile was suggestive of anaemia of chronic disease, chest radiograph showed consolidation, sputum smears were positive for Mycobacterium tuberculosis, and skin slit smear confirmed leprosy. The patient was prescribed WHO recommended multidrug therapy for multibacillary leprosy with three drugs. Additionally, prednisolone was added to her regimen for 2 weeks to treat the type 2 lepra reaction. For treatment of TB, she was placed on the standard 6-month short course chemotherapy. She was lost to follow-up, and attempts were made to contact her. Later, it came to our notice that she had discontinued medications and passed away 3 months after diagnosis.
BACKGROUND: Dental laboratory technicians are at risk of developing occupational respiratory diseases due to exposure to various potentially toxic substances in their working environment. Since 1939, few cases of silicosis among dental technician have been reported.
CASE PRESENTATION: We illustrate a 38 year-old female, who worked in a dental laboratory for 20 years, initially treated as pulmonary tuberculosis and chronic necrotising aspergillosis without much improvement. Computed tomography guided lung biopsy and bronchoscopic transbronchial lung biopsy were performed. Lung tissue biopsies showed presence of refractile dental materials within the areas of histiocyte proliferation. The diagnosis of dental technician pneumoconiosis was obtained and our patient underwent pulmonary rehabilitation.
CONCLUSIONS: This case highlights the importance of obtaining a detailed occupational history in tuberculosis endemic area, as pulmonary tuberculosis is a great mimicker of other respiratory diseases.
BACKGROUND: Tuberculosis (TB) is generally well controlled in Malaysia, but remains an important problem in the nation's eastern states. In order to better understand factors contributing to high TB rates in the eastern state of Sabah, our aims were to describe characteristics of patients with TB at a large outpatient clinic, and determine the prevalence of HIV co-infection. Additionally, we sought to test sensitivity and specificity of the locally-available point-of-care HIV test kits.
METHODS: We enrolled consenting adults with smear-positive pulmonary TB for a 2-year period at Luyang Clinic, Kota Kinabalu, Malaysia. Participants were questioned about ethnicity, smoking, prior TB, disease duration, symptoms and comorbidities. Chest radiographs were scored using a previously devised tool. HIV was tested after counselling using 2 point-of-care tests for each patient: the test routinely in use at the TB clinic (either Advanced Quality™ Rapid Anti-HIV 1&2, FACTS anti-HIV 1/2 RAPID or HIV (1 + 2) Antibody Colloidal Gold), and a comparator test (Abbott Determine™ HIV-1/2, Inverness Medical). Positive tests were confirmed by enzyme immunoassay (EIA), particle agglutination and line immunoassay.
RESULTS: 176 participants were enrolled; 59 (33.5%) were non-Malaysians and 104 (59.1%) were male. Smoking rates were high (81/104 males, 77.9%), most had cavitary disease (51/145, 64.8%), and 81/176 (46.0%) had haemoptysis. The median period of symptoms prior to treatment onset was 8 weeks. Diabetes was present in 12. People with diabetes or other comorbidities had less severe TB, suggesting different healthcare seeking behaviours in this group. All participants consented to HIV testing: three (1.7%) were positive according to Determine™ and EIA, but one of these tested negative on the point-of-care test available at the clinic (Advanced Quality™ Rapid Anti-HIV 1&2). The low number of positive tests and changes in locally-available test type meant that accurate estimates of sensitivity and specificity were not possible.
CONCLUSION: Patients had advanced disease at diagnosis, long diagnostic delays, low HIV co-infection rates, high smoking rates among males, and migrants may be over-represented. These findings provide important insights to guide local TB control efforts. Caution is required in using some point-of-care HIV tests, and ongoing quality control measures are of major importance.
Study site: Klinik Kesihatan Luyang (Tuberculosis Clinic), Kota Kinabalu, Sabah, Malaysia,
OBJECTIVE: To systematically review Indian literature on delays in tuberculosis (TB) diagnosis and treatment.
METHODS: We searched multiple sources for studies on delays in patients with pulmonary TB and those with chest symptoms. Studies were included if numeric data on any delay were reported. Patient delay was defined as the interval between onset of symptoms and the patient's first contact with a health care provider. Diagnostic delay was defined as the interval between the first consultation with a health care provider and diagnosis. Treatment delay was defined as the interval between diagnosis and initiation of anti-tuberculosis treatment. Total delay was defined as time interval from the onset of symptoms until treatment initiation.
RESULTS: Among 541 potential citations identified, 23 studies met the inclusion criteria. Included studies used a variety of definitions for onset of symptoms and delays. Median estimates of patient, diagnostic and treatment delay were respectively 18.4 (IQR 14.3-27.0), 31.0 (IQR 24.5-35.4) and 2.5 days (IQR 1.9-3.6) for patients with TB and those with chest symptoms combined. The median total delay was 55.3 days (IQR 46.5-61.5). About 48% of all patients first consulted private providers; an average of 2.7 health care providers were consulted before diagnosis. Number and type of provider first consulted were the most important risk factors for delay.
CONCLUSIONS: These findings underscore the need to develop novel strategies for reducing patient and diagnostic delays and engaging first-contact health care providers.
Mycobacterium tuberculosis, the causing agent of tuberculosis, comes second only after HIV on the list of infectious agents slaughtering many worldwide. Due to the limitations behind the conventional detection methods, it is therefore critical to develop new sensitive sensing systems capable of quick detection of the infectious agent. In the present study, the surface modified cadmium-telluride quantum dots and gold nanoparticles conjunct with two specific oligonucleotides against early secretory antigenic target 6 were used to develop a sandwich-form fluorescence resonance energy transfer-based biosensor to detect M. tuberculosis complex and differentiate M. tuberculosis and M. bovis Bacille Calmette-Guerin simultaneously. The sensitivity and specificity of the newly developed biosensor were 94.2% and 86.6%, respectively, while the sensitivity and specificity of polymerase chain reaction and nested polymerase chain reaction were considerably lower, 74.2%, 73.3% and 82.8%, 80%, respectively. The detection limits of the sandwich-form fluorescence resonance energy transfer-based biosensor were far lower (10 fg) than those of the polymerase chain reaction and nested polymerase chain reaction (100 fg). Although the cost of the developed nanobiosensor was slightly higher than those of the polymerase chain reaction-based techniques, its unique advantages in terms of turnaround time, higher sensitivity and specificity, as well as a 10-fold lower detection limit would clearly recommend this test as a more appropriate and cost-effective tool for large scale operations.
At present, much of the attention within tuberculosis (TB) management is spent on microbiological cure, and its impact on health-related quality of life (HRQoL) is either undervalued or seldom considered. The aim of this study was to evaluate the impact of TB treatment on HRQoL of new smear positive pulmonary tuberculosis (PTB) patients. Moreover, we also aimed to determine whether the selected socio-demographic and clinical variables were predictive of variability in the HRQoL scores over time.
Delays in tuberculosis (TB) diagnosis, particularly in prisons, is associated with detrimental outcomes. The new GeneXpert MTB/RIF assay (Xpert) offers accurate and rapid diagnosis of active TB, but its performance in improving case detection in high-transmission congregate settings has yet to be evaluated. We assessed the diagnostic accuracy of a single Xpert assay in an intensified case finding survey among HIV-infected prisoners in Malaysia.
Dermatomyositis is a rare rheumatic disease which predominantly affects the muscles and skin requiring a protracted course of immunosuppressants which may predispose the patients to opportunistic infections. A 49-year-old lady was diagnosed to have dermatomyositis in August 2010 based on history, significantly raised creatine kinase level and muscle biopsy findings. She had recurrent admissions due to fever, myalgia and muscle weakness. She had spiking temperature despite high dose steroids, broad-spectrum antibiotics and antifungal agents. This prompted extensive investigation which leads us to the additional diagnosis of disseminated tuberculosis involving the lungs, muscles and bones. This case demonstrates the challenge in controlling the disease activity of dermatomyositis with immunosuppressants in the setting of disseminated tuberculosis.
This was an eight year (2000-2007) retrospective study of tuberculosis in patients admitted to the UMMC. A total of 131 cases were analyzed. Malays constituted the most cases, (43%), followed by Chinese (22%), Indians (17%) and others (18%). The majority of cases were within the 21-60 year old age group, which constituted 69.5% of the total. Males were more commonly affected (65%). Most cases were reported among Malaysians (83%). The majority of patients were unemployed (39%), followed by housewives (10%), laborers (9%), students (8%), shop assistants (7%), and other occupations (27%). The most common presenting complaints were prolonged productive cough, night sweats, fever, anorexia, weight loss (57%), hemoptysis (34%), and undifferentiated symptoms, such as prolonged diarrhea and dysphagia (9%). Sputum was positive for acid-fast bacilli (AFB) in 89%, but only 69% of cases had abnormal chest radiographs. The majority of patients (65%) developed no complications. The most common complications were pleural effusion, pneumothorax and pulmonary fibrosis. The majority of patients (82%) suffered either from diabetes mellitus, hypertension, ischemic heart disease or all 3 conditions. Regarding risk factors for tuberculosis, two were HIV positive and two were intravenous drug users. The majority of the patients (85%) did not complain of any side effects from their anti-tuberculosis treatment. Among those who did complain of side effects, the most common were nausea and vomiting (41%), drug induced hepatitis (37%), blurring of vision (11%) and skin rashes (11%). Two cases of death were reported.
A prospective study was conducted on 510 respiratory specimens for the presence of M. tuberculosis detected by direct acid-fast bacilli (AFB) smear examination, culture in the Manual Mycobacteria Growth Indicator Tube (BBL MGIT, Becton-Dickinson) and culture on Lowenstein-Jensen (LJ) medium. From positive BBL MGIT tubes, Ziehl-Neelsen and Gram stains were performed and subcultures were put up on LJ medium. A total of 101 (19.8%) specimens were positive by the BBL MGIT, 60 (11.8%) by primary LJ medium culture, 31 (6.1%) by direct smear examination and 29 (5.7%) by all three methods. Using primary LJ culture as the gold standard, the sensitivity and specificity of the BBL MGIT were 90% and 89.6% respectively but the sensitivity of AFB smear microscopy was only 48.3%. About half (51.1%) of the BBL MGIT false positives were due to contamination by non-AFB bacteria. The remaining false positives comprised specimens that were AFB microscopy positive but LJ culture negative. Of the AFB isolates obtained on LJ primary and sub-cultures, almost all (93.3%) were identified as Mycobacterium tuberculosis complex. The mean time-to-detection was significantly shorter (p < 0.0001) for the BBL MGIT than for LJ culture. For the former, positive results were available within 14 days for both AFB smear-positive and AFB smear-negative specimens. On the average, positive results were obtained 1.8 days earlier for direct AFB smear-positive samples than for AFB smear-negative samples. On the other hand, positive growth on LJ medium appeared after at least 33 days of incubation. These findings suggest that the BBL MGIT system will be a suitable alternative to LJ culture for the routine diagnosis of pulmonary tuberculosis, but a combination of liquid and solid cultures is still required for the highest diagnostic accuracy.
Delayed diagnosis of tuberculosis (TB) can lead to an increased period of infectivity in the community, a delay in treatment and a severe form of the disease. The objective of this study was to determine the length of delay, and factors linking the delay from the onset of symptoms of pulmonary tuberculosis (PTB) until the commencement of treatment in Sarawak, Malaysia.
The aims of this study were to investigate the frequency of Mycobacterium tuberculosis as a cause of community-acquired pneumonia (CAP) requiring hospitalization in Malaysia, and to define the clinical features of pulmonary tuberculosis (PTB) that distinguish it from non-TB CAP.
Tuberculosis (TB) remains a public health problem in Malaysia. We describe three atypical cases of serious tuberculosis in children. The potential diagnostic pitfall in these cases is highlighted by its unusual presentation in a setting of culture-negative infection. A positive polymerase chain reaction (PCR) in each case assists in gauging the diagnosis in concordance with appropriate clinical findings.
Delay in commencing treatment in patients diagnosed with smear-positive pulmonary tuberculosis (PTB) may promote the spread of PTB in the community. Socio-demographic and clinical data from 169 patients (119 retrospectively and 50 prospectively collected) treated for smear-positive PTB in our hospital Chest Clinic from June 2002 to February 2003 were analysed. One hundred and fifty eight (93.5%) patients were started on treatment in less than 7 days from the time when the report first became available while 11 (6.5%) patients had their treatment started > or = 7 days. The median 'discovery to treatment' window was 1 day (range, 0 to 24 days). Of the factors studied, longevity of symptoms, absence of fever or night sweats and having sought traditional medicine were associated with delay in treatment commencement. The urgency and importance of anti-TB treatment should be emphasized especially to patients who are inclined towards treatment with traditional medicine.
Keywords: Smear positive, pulmonary tuberculosis, treatment delay, traditional medicine, Malaysia, Seremban, Negeri Sembilan