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.
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.
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.
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.
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.
In this retrospective study, we investigated 263 foreign patients who were diagnosed as having tuberculosis at the National Tuberculosis Center (NTBC) from January 2001 to December 2002. The age range was 14-72 years, with a mean of 33.3 +/- 9.95 years. The study subjects were predominantly males (60%) and females comprised 40%, where the greater impact of tuberculosis was observed in the young and active ones (up to 34 years of age), than middle-age (up to 54). A significantly higher percentage of these patients were from the Southeast Asian countries (87%) and particularly occurred in single male (47.5%) and married female (71.4%) patients (p<0.05). We also found that tuberculosis was significantly higher in female (50.5%) and male (64%) with smoking laborers (p<0.05). Fever (70%), cough (90.5%) and BCG vaccination status showed a significantly higher percentage in male patients (p<0.05), whereas lymphadenopathy (22%) was found in a significantly higher percentage in females (p<0.05). Overall, pulmonary disease (94.3%) occurred more commonly in males and the pleura (3.2%) was the most common site of disseminated tuberculosis. By contrast, the lymph node (11.4%) and miliary (4.8%) forms were the more common extrapulmonary tuberculosis in females. More males had higher percentage of treatment completed at > or = 6 (38%) and > or = 9 (13.3%) months in pulmonary tuberculosis, whilst, more females showed higher percentage of treatment completed (8.7%) in extrapulmonary tuberculosis. Surprisingly, more women showed non-compliance to the anti-tubercular therapy than their counterpart in this study.
To characterize the demographic profiles, clinical features, radiological patterns and outcomes of treatment of HIV-infected TB patients, a descriptive study was carried out on 149 HIV-infected TB cases diagnosed from 1998 through 2001 at Kota Bharu Hospital, Kelantan, Malaysia. The majority of the patients were males (94.6%), single (45.0%), ethnic Malay (94.0%) with a mean age of 34 years (standard deviation 7.8, range 18-76). The most common HIV transmission category was through injecting drug use (73.8%) and being the inmates or former inhabitants of drug rehabilitation centers and prisons were the commonest high-risk groups. One hundred and seventeen patients were diagnosed as having pulmonary TB, while about 20% were extra-pulmonary in type with 9 cases of milliary TB. The majority (45%) presented with cough symptoms while only 51% had a positive sputum smear. Fifty-five percent were found to have pulmonary lesions on chest x-ray, such as localized, milliary or diffuse pulmonary infiltrates, or opacities. Eight (5.4%) had pleural lesions while another 8 cases had hilar or mediastinal lymph node lesions. Overall, fifty-eight (38.9%) patients had died by the completion of data collection. The median weeks or survival from the time of starting TB treatment was 13.5 (range 1-56) and the majority of them (74%) died without completing the 6-month regime of treatment.
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
The diagnosis of pulmonary tuberculosis is often delayed due to atypical clinical features and difficulty in obtaining positive bacteriology. We reviewed 232 cases of pulmonary tuberculosis diagnosed in Kedah Medical Centre, Alor Setar from January 1998 to December 2002. All age groups were affected with a male predominance (Male:Female ratio = 60:40). Risk factors include underlying diabetes mellitus (17.7%), positive family history (16.8%) and previous tuberculosis (5.2%). Nearly half (45.3%) of patients had symptoms for more than one year. Only 22% of patients had typical symptoms of tuberculosis (prolonged recurrent fever, cough, anorexia and weight loss), whilst others presented with haemoptysis, chronic cough, COPD, bronchiectasis, general ill-health, pyrexia of unknown origin or pleural effusion without other systemic symptoms. Fifteen percent of the patients presented with extrapulmonary diagnosis. Ninety percent of the patients had previous medical consultations but 40% had no chest radiograph or sputum examination done. The chest radiographs showed 'typical' changes of tuberculosis in 62% while in the other 38% the radiological features were 'not typical'. Sputum direct smear was positive for acid-fast bacilli in only 22.8% of patients and 11.2% were diagnosed base on positive sputum culture. Sputum may be negative even in patients with typical clinical presentations and chest radiograph changes. Bronchial washing improved the diagnosis rate being positive in 49.1% of cases (24.1% by direct smear and the other 25.0% by culture). In 16.8% of cases, the diagnosis was based on a good response to empirical anti-tuberculosis therapy in patients with clinical and radiological features characteristic of tuberculosis. In conclusions, the clinical and radiological manifestations of pulmonary tuberculosis may be atypical. Sputum is often negative and bronchoscopy with washings for Mycobacterium culture gives a higher yield for diagnosis. In highly probable cases, empirical therapy with antituberculosis drugs should be considered because it is safe and beneficial.
Pulmonary disease is sometimes treated empirically as tuberculosis (TB) in the absence of microbial confirmation if the clinical suspicion of active TB is high. In a country of relatively high TB and low HIV burden, we retrospectively studied 107 patients (69.2% male; mean age (SD): 45 (17) years) who received empirical anti-TB treatment for intrapulmonary opacities or pleural effusions suspected of active TB in our hospitals between 1998 and 2002. The diagnosis of definite or probable 'smear-negative' pulmonary TB was made based on treatment outcome at two months with rifampicin, isoniazid, pyrazinamide and ethambutol (or streptomycin). At this end-point, 81 patients (84.4%) had both clinical and radiological improvement (definite cases), 12 (12.5%) had clinical improvement alone and 3 (3.1%) had radiological improvement alone (probable cases). Confirmation of acid-fast bacilli was subsequently obtained in 12 patients (all definite cases) from culture of initial pulmonary specimens. Eleven patients (10.5%) were diagnosed as 'non-TB' based on absence of both clinical and radiological improvement or discovery of another cause for the pulmonary condition at or before this two-month study end-point. In the 'non-TB' group, 2 had carcinoma, 2 had HIV-related pulmonary diseases, 1 had bronchiectasis, while in 6 causes were indeterminate. Six (6.3%) and 3 (27.3%) patients reported adverse effects from anti-TB drugs from the 'TB' and 'non-TB' groups respectively. Our findings suggest that empirical anti-TB treatment is an acceptable practice if clinical suspicion is high in patients coming in our region.
The process of case-finding was studied in 100 consecutive patients with pulmonary tuberculosis treated by the Chest Clinic, Penang Hospital. The median time from the onset of the illness until the initial medical consultation was two weeks (patient's delay). This delay was longer in males, patients with lower than secondary education and drug abusers. Only 47% of patients were put on treatment with a correct diagnosis within one month of the first consultation (doctor's delay). Almost all patients had at least one symptom suggestive of tuberculosis at presentation and the mean number of consultations before diagnosis was three. Patients who first visited government medical facilities had shorter doctor's delay than those who first saw private practitioners, and patients who first consulted a private practitioner were the least likely to be appropriately investigated by sputum examination and chest radiography. The median total delay was three months and at the time of diagnosis, 95% of patients had moderate or far advanced disease radiologically. In order to shorten doctor's delay, all medical practitioners, especially those in the private sector, should be made aware of the importance of early diagnosis and the proper management of tuberculosis. Health education campaigns for the public should also be undertaken to shorten patient's delay.
Study site: Chest clinic, Hospital Pulau Pinang, Malaysia
The role of fiberoptic bronchoscopy for rapid diagnosis of pulmonary tuberculosis was examined among 74 patients who were suspected of having the disease but had negative sputum smear for acid fast bacilli. Bronchial brushing and washing were routinely performed in all subjects and bronchial biopsy was performed on abnormal mucosa in 7 of them. The diagnosis of pulmonary tuberculosis was confirmed in 44.6% of the patients studied from smear examination, culture, histology or the combination of them. Rapid diagnosis was achieved in 54.5% of the confirmed cases from smear or histology within a few days of examination. Two of the cases had concomitant bronchogenic carcinoma. We conclude that the fiberoptic bronchoscopy is a useful investigation for this group of patients as confirmation of the diagnosis can be made fairly rapidly in a significant proportion of them, hence the treatment can be started confidently.
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.
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.
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.
We reviewed the 52 new cases of pulmonary tuberculosis diagnosed at Pusat Pakar Utara, Kedah in 1998. It was found that the majority of the patients had symptoms for many years. They had seen many doctors but were not diagnosed. In 40% of the patients, no investigations for tuberculosis were done and in the others tuberculosis was excluded because of negative sputum smear examination. Many had typical history and X-ray changes suggestive of tuberculosis but more sensitive investigations such as sputum culture for Mycobacterium or bronchoscopy were not performed. Cases are presented to illustrate the problems in the diagnosis.