Smear-negative Tuberculosis Cases Research Articles

Study of rapid detection of Mycobacterium Tuberculosis through GeneXpert MTB/RIF assay from acid fast bacilli smear-negative specimens in a Tertiary Care Hospital, Biratnagar Nepal

Introduction: Tuberculosis (TB) is an important public health concern around the world. It is well known that acid-fast bacilli (AFB) smear-negative TB cases are a major source of spreading TB to others when left untreated.
 Objectives: Our study aim to detect Mycobacterium tuberculosis (MTB) in AFB smear-negative samples through GeneXpert MTB/RIF assay and also to evaluate the drug resistance patterns towards Mycobacterium tuberculosis in hospitals.Methodology: This descriptive cross-sectional study was conducted among smear-negative presumptive TB patients at a tertiary care center with effect from September 2022 to September 2023 after approval from the Institutional Review Committee of the college. A convenience sampling method was used.
 Results: Out of 653 smear-negative samples, 71 (10.9%) were positive for TB and 17 (2.6%) were rifampicin resistance cases detected by GeneXpert MTB/RIF assay. The cases of tuberculosis were more in age groups between 46->60 years and least in 17-30 years of age. Pulmonary samples yielded a higher number of MTB 66 (92.95%) as compared to extra-pulmonary samples 5 (7.04%). There is an almost equal proportion of mycobacterium infection in males 37(52.11%) and females 34(47.88%). All the rifampicin resistance cases detected in our study were from pulmonary samples.
 Conclusion: Our study shows that the sensitivity of GeneXpert MTB/RIF assay is higher than AFB smear microscopy. We are missing actual TB cases while using AFB smear microscopy only. Hence the GeneXpert MTB/RIF assay is important for the rapid detection of MTB in smear-negative as well as smear-positive drug resistance MTB cases.

Gene-Based Diagnosis of Tuberculosis from Oral Swabs with a New Generation Pathogen Enrichment Technique.

ABSTRACTA rapid and sensitive diagnosis is crucial for the management of tuberculosis (TB). A simple and label-free approach via homobifunctional imidoesters with a microfluidic platform (SLIM) assay showed a higher sensitivity than the Xpert MTB/RIF assay in the diagnosis of pulmonary TB (PTB). Here, we evaluated the efficacy of the SLIM assay for oral swab samples from cases of suspected PTB. Patients with clinically suspected PTB were prospectively enrolled and oral swab samples were processed using the SLIM assay and the attending physicians were blinded to the results of the SLIM assay. TB cases were defined as those treated with anti-TB chemotherapy for at least 6 months at the discretion of the specialists based on their clinical features and conventional laboratory results, including the Xpert assay. A total of 272 patients (with TB, n = 128 [47.1%]; without TB, n = 144 [52.9%]; mean age, 59.8 years) were enrolled. Overall, the sensitivity of the oral swab-based SLIM assay (65.6%) was higher than that of the sputum-based Xpert assay (43.4%; P = 0.001). Specifically, the SLIM oral swab assay showed a notably higher sensitivity in culture-negative TB cases compared with the Xpert assay (69.0% [95% CI: 49.2 to 84.7%] versus 7.4% [95% CI: 0.9 to 24.3%]; P = 0.001). The specificity of the SLIM and the Xpert assays was 86.1% (95% CI: 79.3 to 91.3%) and 100% (95% CI: 97.2 to 100%), respectively. When only culture-confirmed cases were analyzed, the SLIM oral swab was comparable to sputum Xpert in sensitivity (64.7% versus 54.3%, P = 0.26). The oral swab-based SLIM assay showed a superior sensitivity for TB diagnosis over the sputum-based Xpert assay, especially for culture-negative cases.IMPORTANCE The development of a rapid, accessible, and highly sensitive diagnostic tool is a major challenge in the control and management of tuberculosis. Gene-based diagnostics is recommended for the rapid diagnosis of pulmonary tuberculosis (PTB), but its sensitivity, such as Xpert MTB/RIF assay (Xpert), drops in cases with a low bacterial load. It can only be applied to sputum samples, and it is quite difficult for some patients to produce an adequate amount of sputum. We evaluated the clinical validity of an oral swab-based microfluidic system, i.e., the SLIM assay. The SLIM assay showed a significantly higher sensitivity than the Xpert assay, especially in smear-negative TB cases. This non-sputum-based SLIM assay can be a useful diagnostic test by overcoming the limitations of conventional sputum-based tests in pulmonary TB.

Decline of Tuberculosis Burden in Vietnam Measured by Consecutive National Surveys, 2007-2017.

Vietnam, a high tuberculosis (TB) burden country, conducted national TB prevalence surveys in 2007 and 2017. In both surveys participants were screened by using a questionnaire and chest radiograph; sputum samples were then collected to test for Mycobacterium tuberculosis by smear microscopy and Löwenstein-Jensen culture. Culture-positive, smear-positive, and smear-negative TB cases were defined by laboratory results, and the prevalence of tuberculosis was compared between the 2 surveys. The results showed prevalence of culture-positive TB decreased by 37% (95% CI 11.5%–55.4%), from 199 (95% CI 160–248) cases/100,000 adults in 2007 to 125 (95% CI 98–159) cases/100,000 adults in 2017. Prevalence of smear-positive TB dropped by 53% (95% CI 27.0%–69.7%), from 99 (95% CI 78–125) cases/100,000 adults to 46 (95% CI 32–68) cases/100,000 adults; smear-negative TB showed no substantial decrease. Replacing microscopy with molecular methods for primary diagnostics might enhance diagnosis of pulmonary TB cases and further lower TB burden.

Decline of Tuberculosis Burden in Vietnam Measured by Consecutive National Surveys, 2007–2017

Abstract Vietnam, a high tuberculosis (TB) burden country, conducted national TB prevalence surveys in 2007 and 2017. In both surveys participants were screened by using a questionnaire and chest radiograph; sputum samples were then collected to test for Mycobacterium tuberculosis by smear microscopy and Löwenstein-Jensen culture. Culture-positive, smear-positive, and smear-negative TB cases were defined by laboratory results, and the prevalence of tuberculosis was compared between the 2 surveys. The results showed prevalence of culture-positive TB decreased by 37% (95% CI 11.5%–55.4%), from 199 (95% CI 160–248) cases/100,000 adults in 2007 to 125 (95% CI 98–159) cases/100,000 adults in 2017. Prevalence of smear-positive TB dropped by 53% (95% CI 27.0%–69.7%), from 99 (95% CI 78–125) cases/100,000 adults to 46 (95% CI 32–68) cases/100,000 adults; smear-negative TB showed no substantial decrease. Replacing microscopy with molecular methods for primary diagnostics might enhance diagnosis of pulmonary TB cases and further lower TB burden.

Use of Xpert Contributes to Accurate Diagnosis, Timely Initiation, and Rational Use of Anti-TB Treatment Among Childhood Tuberculosis Cases in South Central Ethiopia.

BackgroundChildhood tuberculosis (TB) was under-prioritized, and only 15% of childhood TB cases are microbiologically confirmed. Hence, most childhood TB diagnoses are made on a clinical basis and prone to over- or under-treatment. Xpert is a rapid method for the diagnosis of childhood TB with high sensitivity.ObjectiveTo assess the use of Xpert for accurate diagnosis, timely initiation, and rational use of anti-TB treatment among childhood TB.MethodsIn 2016, the hospital facilitated the installation of the Xpert machine. We reviewed data trends over four consecutive years; two years before the arrival of the machine and two years following the implementation of Xpert. Data were extracted retrospectively from electronically stored databases and medical records and entered to SPSS 21 for analysis.ResultsIn the pre-intervention period (2014–2015), 404 cases of children presenting with symptoms or signs suggestive of TB (“presumptive TB”) were evaluated using AFB microscopy. A total of 254 (62.8%) TB diagnoses were made, of which 54 (21.3%) were confirmed by smear AFB while 200 (78.7%) were treated as smear-negative TB cases. The mean waiting time to start anti-TB treatment was 6.95 days [95% CI (3.71–10.90)]. During the intervention period (2016–2017), 371 children with presumptive TB were evaluated using Xpert. A total of 199 (53.6%) childhood TB cases were notified, of which 88 (44.2%) were Xpert positive and 111 (55.8%) were treated as Xpert-negative probable TB cases. The tendency to initiate anti-TB treatment for unconfirmed TB cases was reduced by a third. Compared with smear AFB, Xpert improved accuracy of diagnosing pediatric TB cases two-fold. The average waiting time to start anti-TB treatment was 1.33 days [95% CI (0.95–1.71)]. There was a significant reduction in the waiting time to start anti-TB treatment, with a mean time difference before and during intervention of 5.62 days [95% CI (1.68–9.56)].ConclusionXpert use was associated with a significant increase in the accuracy of identifying confirmed TB cases, reduced unnecessary anti-TB prescription, and shortened the time taken to start TB treatment.

National population-based tuberculosis prevalence survey in Ghana, 2013.

BACKGROUND: The prevalence of tuberculosis (TB) disease is one of the three main indicators used to assess the epidemiological burden of TB and the impact change of TB control; the other two are incidence and mortality.OBJECTIVE: To estimate the prevalence of TB disease among adults in Ghana.METHODS: A nationally representative cross-sectional survey was conducted. Participants were screened for TB using interview and chest X-ray (CXR). For those participants with cough ≥2 weeks and/or abnormal CXR, spot and morning sputum specimens were collected and examined by smear microscopy and culture.RESULTS: The study revealed that the prevalence of smear-positive TB among adults (age ≥15 years) was 111 (95%CI 76-145) and that of bacteriologically confirmed TB was 356 (95%CI 288-425) per 100 000 population. Males and older people had a higher prevalence than their counterparts. The majority of TB cases were smear-negative and had an abnormal CXR without reported chronic cough.CONCLUSION: The survey revealed much higher TB disease burden than previously estimated. This implies that the programme needs more effort and resources to find undiagnosed and unreported cases. The higher proportion of smear-negative and asymptomatic TB cases suggests the need to revise the existing screening and diagnostic algorithms.

Comparing diagnostic accuracy of CB-NAAT and ZN staining in diagnosis of Pulmonary and Extra-pulmonary Tuberculosis cases at tertiary care teaching hospital of north India.

Background: Continuing the fight to eradicate tuberculosis from India, which has 24 per cent of the world’s total number of TB cases, is a big challenge for the country to achieve its goal of being TB free by 2025. Keeping in view limitation of culture and smear microscopy, a rapid, accurate, point-of-care diagnostic test that is affordable and can be readily implemented is urgently needed. In recent years, cartridge based nucleic acid amplification test (CBNAAT) has been recommended by World Health Organization as a rapid diagnostic test for detection of tuberculosis and rifampicin resistance. In our study we have tried to analyse whether this has proved as a first critical step in controlling tuberculosis. Aim : In this study, we retrospectively compared results for diagnosis of suspected pulmonary and Extrapulmonary tuberculosis cases, from September 2017 to January 2018 for Ziehl-Neelsen (ZN) and GeneXpert (Xpert® MTB/Rif assay) taking culture as gold standard, in the Department of Microbiology DRPGMC&H Kangra at Tanda. Methods: Performance of Xpert was compared to acid-fast microscopic examination using Ziehl-Neelsen (ZN) stain in patients with culture-confirmed tuberculosis. Results:: Out of total 914 specimens of clinically suspected patients of tuberculosis of all age groups ,683(75%) were pulmonary specimens and231(25%)were extrapulmonary .For pulmonary samples, the sensitivity and specificity for CBNAAT samples were 82.3% and 98.5% while that for sputum smear were 63.7% and 99.3%% respectively. For extrapulmonary samples, the sensitivity and specificity for CBNAAT samples were 85.7% and 93.5% respectively; while that for sputum smear were 60.7% and 100% respectively. Conclusion: Although the development of the Xpert MTB/RIF assay is undoubtedly a landmark event in a high TB burden country like India as this test will help in rapid diagnosis of smear-negative and rifampicin resistant TB cases, which were earlier a challenge for the TB control programmes Key Words: Tuberculosis (TB) Cartridge based nucleic acid amplification test (CBNAAT) Rifampicin (RIF),Mycobacterium tuberculosis(MTB),Ziehl Neelsen(ZN)

Valuing the use of GeneXpert test as an unconventional approach to diagnose pulmonary tuberculosis

BackgroundA rapid, highly sensitive, and qualitative diagnostic test will significantly reduce the incidence of tuberculosis (TB). GeneXpert test is the test that is supposed to play this role with those specifications.ObjectiveOur goal was to assess the precision of the GeneXpert test in the diagnosis of pulmonary TB.Patients and methodsThis cross-sectional analytic study was carried out at Assiut University Hospital in collaboration with Assiut Chest Hospital, Assiut, Egypt. A total of 67 patients of suspected pulmonary TB were included. For microbiological examination, two sputum samples were obtained from each patient within the same day. One sample was collected at Assiut University Hospital and subjected to smear microscopy by Ziehl—Neelsen staining and culture on Lowenstein—Jensen media. The other sample was taken at Assiut Chest Hospital to be processed for GeneXpert Mycobacterium tuberculosis/rifampicin assay. The culture was applied as a confirmatory test to evaluate the Xpert Mycobacterium tuberculosis/rifampicin assay test.ResultsGeneXpert had 95.9% sensitivity and 94.4% specificity in diagnosing pulmonary TB with the area under the curve of 0.95 and overall diagnostic accuracy of 95.5%. Ziehl—Neelsen examination had 65.3% sensitivity and 100% specificity with the area under the curve of 0.83 and overall diagnostic accuracy of 74.6. For smear-negative, culture-positive cases, GeneXpert showed sensitivity of 94.1%. False-positive GeneXpert for TB was recorded in just one patient.ConclusionThe GeneXpert test is accurate in diagnosing pulmonary TB and its greatest benefit is clearly demonstrated in smear-negative TB cases. However, the test is not free from some fallacies, even if they are a few, which draws our attention to the importance of the conventional culture for TB and the clinical correlation.

Treatment Outcomes of Tuberculosis at Asella Teaching Hospital, Ethiopia: Ten Years' Retrospective Aggregated Data.

Directly Observed Treatment Short-course (DOTS) has been one of the major strategies to combat the epidemic of tuberculosis (TB) globally. This study aimed to evaluate TB treatment outcomes between September 2004 and July 2014 under the DOTS program at one of the largest public hospitals in Ethiopia. A retrospective data of TB patients registered at Asella Teaching Hospital between September 2004 and July 2014 were obtained from hospital registry. Treatment outcomes and types of TB cases were categorized according to the national TB control program guideline. Binomial and multinomial logistic regression models were used to analyze the association between treatment outcomes and potential predictor variables. A total of 1,755 TB patients' records were included in the study. Of these, 945 (53.8%) were male, 480 (27.4%) smear-positive TB, 287 (16.4%) HIV positive, and 1,549 (88.3%) new cases. Among 480 smear-positive pulmonary TB cases, 377 (78.5%) patients were cured, 21 (4.40) completed the treatment, 35 (7.3%) transferred out, 19 (4.0%) died, 24 (5.0%) defaulted, and 4 (0.8%) failure. Overall, 398 (82.9%) smear-positive pulmonary TB patients were successfully treated. For smear-negative TB (n = 641) and extrapulmonary TB cases (n = 634), 1,036 (81.3%) completed the treatment and demonstrated favorable response. Taking all TB types into account, 1,434 (81.7%) were considered as successfully treated. In the multivariate binary logistic model, patients in older age group (AOR = 0.386, 95% CI: 0.250-0.596) and retreatment cases (AOR = 0.422, 95% CI: 0.226-0.790) were less likely to be successfully treated compared to younger and new cases, respectively. In multinomial logistic regression, age increment by 1 year increased the risk of death and default of TB patients by 0.05 (adjusted β = 0.05; 95% CI: 0.03, 0.06) and 0.02 (adjusted β = 0.02; 95% CI: 0.01, 0.04). The odds of TB patients who died during treatment were higher among HIV-infected TB patients (adjusted β = 2.65; 95% CI: 1.28, 5.50). The treatment success rate of TB patients was low as compared to the national target. TB control needs to be strengthened for the enhancement of treatment outcome.

Performance of the TB-LAMP diagnostic assay in reference laboratories: Results from a multicentre study

ObjectiveTo evaluate the diagnostic performance of TB-LAMP, a manual molecular tuberculosis (TB) detection method, and provide comparison to the Xpert MTB/RIF assay. MethodsIn a large multicentre study, two sputum samples were collected from participants with TB symptoms in reference laboratories in Peru, South Africa, Brazil, and Vietnam. Each sample was tested with TB-LAMP. The reference standard consisted of four direct smears, four cultures, and clinical and radiological findings. Individuals negative on conventional tests were followed up after 8 weeks. The Xpert MTB/RIF assay was performed on fresh or frozen samples as a molecular test comparison. ResultsA total of 1036 adults with suspected TB were enrolled. Among 375 culture-confirmed TB cases with 750 sputum samples, TB-LAMP detected 75.6% (95% confidence interval (CI) 71.8–79.4%), including 97.9% (95% CI 96.4–99.4%) of smear-positive TB samples and 46.6% (95% CI 40.6–52.7%) of smear-negative TB samples. Specificity in 477 culture-negative participants not treated for TB (954 sputum samples) was 98.7% (95% CI 97.9–99.6%). TB-LAMP test results were indeterminate in 0.3% of cases. ConclusionsTB-LAMP detects nearly all smear-positive and half of smear-negative TB cases and has a high specificity when performed in reference laboratories. Performance was similar to the Xpert MTB/RIF assay.

Rapid detection of Mycobacterium tuberculosis and rifampicin resistance in extrapulmonary tuberculosis and sputum smear-negative pulmonary suspects using Xpert MTB/RIF.

Tuberculosis (TB) is a serious public health problem in developing countries such as Pakistan. Rapid diagnosis of TB and detection of drug resistance are very important for timely and appropriate management of multidrug-resistant TB (MDR-TB). The purpose of this study was to determine the diagnostic efficacy of the Xpert MTB/RIF assay for rapid diagnosis of TB and detection of rifampicin (RIF) resistance in extrapulmonary and smear-negative pulmonary TB suspects. A total of 98 bronchoalveolar lavage fluid (BALF) and 168 extrapulmonary specimens were processed by Xpert MTB/RIF. Culture results are considered as the gold standard for diagnosis of TB, and drug susceptibility testing for detection of RIF resistance. Diagnostic efficacy was measured in terms of sensitivity, specificity and positive and negative predictive values. The Xpert MTB/RIF assay detected 40 (40.8 %) of 98 BALF of presumptive pulmonary TB and 60 (35.7 %) of 168 extrapulmonary specimens. Sensitivity and specificity of the Xpert MTB/RIF assay for detection of TB was 86 and 88.4 %, respectively. The positive predictive value was 71.5 % while negative predictive value was 95.1 %. The Xpert MTB/RIF assay is a rapid and simple technique with high sensitivity and specificity for diagnosing TB and detecting drug resistance in extrapulmonary and smear-negative TB cases.

The dynamic of tuberculosis case finding in the era of the public–private mix strategy for tuberculosis control in Central Java, Indonesia

ABSTRACT Background: The public–private mix (PPM) strategy has strengthened tuberculosis care and control in many countries. Indonesia, a country with a high tuberculosis burden, has a low tuberculosis case detection rate (CDR), despite PPM implementation in 2003. The PPM in Indonesia involves primary healthcare centers, hospitals, and specialized chest clinics. The long-term impact of the strategy is unknown. Objective: We aimed to explore the case detection achievements of the tuberculosis program since PPM implementation in Central Java in 2003. Methods: This retrospective cohort study covered the period 1 January 2000 to 31 December 2014. The data from tuberculosis patients treated in all health facilities in Central Java implementing directly observed treatment short-course, recorded via a standardized form, were analyzed after being validated by the Office of Health of Central Java Province. We evaluated the CDR, case notification rate, and total number of cases, using linear regression to analyze the temporal trends of those indicators in the phases of PPM implementation. Results: The CDR increased during the initial phase (2000–2005), decreased during the mid-phase (2006–2009), and increased slightly during the late phase (2010–2014), ranging from 13 to 61.72. These trends were observed despite a steady increase in the number of participating healthcare facilities. The regression analysis showed that the CDR of referral institutions contributed the most to the total CDR of Central Java Province. Many of the smear-negative tuberculosis cases recorded at primary healthcare centers may have been smear positive; this probable misclassification could have been partially avoided if more specific and sensitive diagnostic tools were available. Conclusions: The CDR remains below the national target (70%). Early awareness of a negative trend in certain program indicators is important to ensure program sustainability. Careful observation of the indicator pattern will secure the long-term success of the program.

Dilemma in TB diagnostic testing; phenotypic or genotypic testing

Testing for tuberculosis (TB) is difficult because there are so many tests available. Except for the culture-based tests, all others are for screening or add-on tests. On the other hand, there is an urgent need to develop a rapid TB diagnostic test with good sensitivity and specificity.The introduction of liquid culture medium in 1980 (BACTEC 460 radiometric) and later MGIT was a great improvement in a definitive diagnosis, but still results are not as fast as needed. After the discovery of IS6110 sequence and the whole genome sequence of Mycobacterium tuberculosis (MTB) many rapid diagnostic tests have been developed based on the molecular platform. This brought hope that these molecular tests will be the answer to the need for an ideal rapid test for diagnosis and drug susceptibility testing (DST). Among these notable molecular tests are Hain’s LPA and Cepheid’s GeneXpert–GeneXpert being the leading one. Time to results for detection and DST, which used to take 6–8weeks with solid media, was reduced to 4weeks by the BACTEC method and now to 2h by the GeneXpert.Despite significant improvement in the time to report, molecular-based tests still face many challenges. Sensitivity and specificity of a diagnostic test is critical in infectious diseases. For molecular tests lack of sensitivity in smear-negative TB cases is a great concern. In case of DST it is important to have a test which can detect resistance to first-line and most of the second-line drugs with high sensitivity and specificity. At present the genotypic tests are applicable for only a few drugs, while GeneXpert detects only Rifampicin resistance. Because of these limitations, genotypic tests are considered as good screening tests. Until the molecular tests are made more sensitive for the detection of TB and more knowledge is acquired on molecular mechanisms of drug resistance, these tests will remain as screening tools.Sustainability is another issue. Presently, funding agencies are supporting the high cost of the genotypic tests, but what if these funds dry out? This overall situation has created a dilemma of what should be the right option in choosing a TB diagnostic test. Efforts are being made to improve the sensitivity and specificity of molecular tests. Until then, it appears that phenotypic tests, especially using liquid medium, still remain as the only one offering a comprehensive solution in TB diagnosis and DST. There is still a need for a diagnostic test which is simple, rapid and affordable for the low-income, high-TB prevalence countries, and as comprehensive, sensitive and specific as the liquid culture for TB diagnosis and DST.

Evaluation of TB Case Finding through Systematic Contact Investigation, Chhattisgarh, India.

Rationale. Contact investigation is an established tool for early case detection of tuberculosis (TB). In India, contact investigation is not often conducted, despite national policy, and the yield of contact investigation is not well described. Objective. To determine the yield of evaluating household contacts of sputum smear-positive TB cases in Rajnandgaon district, Chhattisgarh, India. Methods. Among 14 public health care facilities with sputum smear microscopy services, home visits were conducted to identify household contacts of all registered sputum smear-positive TB cases. We used a standardized protocol to screen for clinical symptoms suggestive of active TB with additional referral for chest radiograph and sputa collection. Results. From December 2010 to May 2011, 1,556 household contacts of 312 sputum smear-positive TB cases were identified, of which 148 (9.5%) were symptomatic. Among these, 109 (73.6%) were evaluated by sputum examination resulting in 11 cases (10.1%) of sputum smear-positive TB and 4 cases (3.6%) of smear-negative TB. Household visits contributed additional 63% TB cases compared to passive case detection alone. Conclusion. A standard procedure for conducting household contact investigation identified additional TB cases in the community and offered an opportunity to initiate isoniazid chemoprophylaxis among children.

Is Xpert MTB/RIF assay in gastric lavage aspirate useful for diagnosis of smear-negative childhood pulmonary tuberculosis?

This study evaluated the Xpert MTB/RIF assay for diagnosis of smear-negative childhood pulmonary tuberculosis (TB) using gastric lavage aspirates (GLA) in 211 Chinese children. The sensitivity in detecting children with a clinical diagnosis of TB for MGIT and Xpert was 12.1% (95% CI 9.3%, 14.9%) and 48.6% (95% CI 44.4%, 52.8%), respectively. The authors concluded that Xpert MTB/RIF assay is an excellent tool for the diagnosis of smear-negative childhood with GLA samples. The high proportion of very low mycobacterial load in the GLA samples from smear-negative TB cases may increase the frequency for obtaining indeterminate RIF resistance results by Xpert.

Routine programmatic delivery of isoniazid preventive therapy to children in Cape Town, South Africa.

Fourteen primary health care facilities in Cape Town, South Africa. To determine the proportion and characteristics of infectious adult tuberculosis (TB) cases that identify children aged <5 years who qualify for isoniazid preventive therapy (IPT), and to determine the proportion of children who initiate and complete IPT. A retrospective clinical record review conducted as a stratified cluster survey. Of 1179 records of infectious adult cases, 33.3% had no documentation of contacts. Of the remaining 786 records, 525 contacts aged <5 years were identified, representing 0.7 child contacts per infectious adult case. Older age, male, human immunodeficiency virus (HIV) positive, smear-negative and retreatment TB cases were all associated with no documentation of contacts. Of the 525 child contacts identified, less than half were screened for TB, 141 initiated IPT and 19 completed it. Less than 67% of infectious TB case records had documentation of contacts. Younger, female, HIV-negative and new smear-positive TB cases were more likely to have had contacts identified. Less than 14% of children already initiated on IPT completed 6 months of treatment.

Epidemological Association of Tuberculosis and HIV in Visakhapatnam District

The object of our study is to observe the epidemiological distribution and association of Tuberculosis (TB) co-infection with HIV among the Visakhapatnam zone of Andhrapradesh. It is mainly due to Tuberculosis and HIV has been closely linked and HIV infection has contributed to a significant increase in the worldwide incidence of tuberculosis. According to WHO, the proportion of TB cases co-infected with HIV was also found rising being 2- 10 times greater for 1997 estimates than for 1990 2 . By producing a progressive decline in cell-mediated immunity, HIV alters the pathogenesis of tuberculosis, greatly increasing the risk of developing disease in co-infected individuals and leading to more frequent extra pulmonary involvement and atypical radiographic manifestations. In the present analysis it was found that in new smear pulmonary TB cases; there was an increase trend in number of cases in both male and female. According to smear positive and smear negative TB cases, male are more prone to TB (71.77% smear positive and 63.83% smear negative) than female (28.22% smear positive and 36.16% smear negative). In all the TB cases registered through RNTCP 4186 TB Patients are reported to be tested for HIV before or during the treatment. Out of those 4,186 cases, 558 are HIV positive.

THE VALUE OF FLUORESCENT MICROSCOPY AND BLEACH SEDIMENTATION METHOD FOR DETECTION OF SMEAR NEGATIVE TUBERCULOSIS

The diagnosis of tuberculosis in developing countries has been done by direct microscopic examination which has low sensitivity. Most of the patients with TB are detected as free of TB. For the low sensitivity of the directed microscopy, a new high sensitive fluorescent microscope was developed. In addition bleach sedimentation technique increased the sensitivity of both direct and fluorescent techniques. This investigation was undertaken to evaluate the value of fluorescent microscopy and bleach sedimentation method for the detection of smear negative tuberculosis cases in sputum sample in comparison with direct microscopy. A total of 132 sputum samples from patients aged 7 to 75 years were examined during the study period. Culture (Gold standard) result identi- fied 75 subjects as positive. Among 75 cultures positive sputum samples direct Ziehl Neilson technique identified 50 samples as positive with sensitivity of 66% and specificity of 98.2%. In fluorescent microscopy 55 of them were identified as positive with sensitivity of 78.6% and specificity of 80.7% in comparison with culture. On the other hand over night bleach sedimentation in Ziehl Neilson technique has increased the sensitivity to 76% and resulted in specificity of 91.2%. Bleach fluorescent microscopy has increased the sensitivity to 82.7% and resulted in specificity of 80.7% in comparison with culture. From the total of 132 samples 81 were smear negative samples as confirmed by direct microscopy. From these 81 samples direct fluorescent microscopy has identified 12 samples as positive out of 25 culture positive samples with sensitivity of 48% and specificity of 80.3%. Bleach direct microscopy has identified 8 positive with sensitivity of 32% and specificity of 89.3%. Bleach fluorescent microscopy identified 13 as positive with sensitivity of 52% and specificity of 82%. Therefore, the combination of bleach sedimentation and florescent microscopy can be used as a diagnostic tool for the reduction of morbidity and mortality occurring from Tuberculosis and can be used for early diagnosis and treatment of the disease.

Impact of Xpert MTB/RIF Testing on Tuberculosis Management and Outcomes in Hospitalized Patients in Uganda

RationaleThe clinical impact of Xpert MTB/RIF for tuberculosis (TB) diagnosis in high HIV-prevalence settings is unknown.ObjectiveTo determine the diagnostic accuracy and impact of Xpert MTB/RIF among high-risk TB suspects.MethodsWe prospectively enrolled consecutive, hospitalized, Ugandan TB suspects in two phases: baseline phase in which Xpert MTB/RIF results were not reported to clinicians and an implementation phase in which results were reported. We determined the diagnostic accuracy of Xpert MTB/RIF in reference to culture (solid and liquid) and compared patient outcomes by study phase.Results477 patients were included (baseline phase 287, implementation phase 190). Xpert MTB/RIF had high sensitivity (187/237, 79%, 95% CI: 73–84%) and specificity (190/199, 96%, 95% CI: 92–98%) for culture-positive TB overall, but sensitivity was lower (34/81, 42%, 95% CI: 31–54%) among smear-negative TB cases. Xpert MTB/RIF reduced median days-to-TB detection for all TB cases (1 [IQR 0–26] vs. 0 [IQR 0–1], p<0.001), and for smear-negative TB (35 [IQR 22–55] vs. 22 [IQR 0–33], p = 0.001). However, median days-to-TB treatment was similar for all TB cases (1 [IQR 0–5] vs. 0 [IQR 0–2], p = 0.06) and for smear-negative TB (7 [IQR 3–53] vs. 6 [IQR 1–61], p = 0.78). Two-month mortality was also similar between study phases among 252 TB cases (17% vs. 14%, difference +3%, 95% CI: −21% to +27%, p = 0.80), and among 87 smear-negative TB cases (28% vs. 22%, difference +6%, 95% CI: −34 to +46%, p = 0.77).ConclusionsXpert MTB/RIF facilitated more accurate and earlier TB diagnosis, leading to a higher proportion of TB suspects with a confirmed TB diagnosis prior to hospital discharge in a high HIV/low MDR TB prevalence setting. However, our study did not detect a decrease in two-month mortality following implementation of Xpert MTB/RIF possibly because of insufficient powering, differences in empiric TB treatment rates, and disease severity between study phases.

A Diagnostic Accuracy Study of Xpert®MTB/RIF in HIV-Positive Patients with High Clinical Suspicion of Pulmonary Tuberculosis in Lima, Peru

BackgroundDiagnosis of pulmonary tuberculosis (TB) among human immunodeficiency virus (HIV) patients remains complex and demands easy to perform and accurate tests. Xpert®MTB/RIF (MTB/RIF) is a molecular TB diagnostic test which is rapid and convenient; the test requires minimal human resources and reports results within two hours. The majority of performance studies of MTB/RIF have been performed in high HIV burden settings, thus TB diagnostic studies among HIV patients in low HIV prevalence settings such as Peru are still needed.Methodology/Principal FindingsFrom April 2010 to May 2011, HIV-positive patients with high clinical suspicion of TB were enrolled from two tertiary hospitals in Lima, Peru. Detection of TB by MTB/RIF was compared to a composite reference standard Löwenstein-Jensen (LJ) and liquid culture. Detection of rifampicin resistance was compared to the LJ proportion method. We included 131 patients, the median CD4 cell count was 154.5 cells/mm3 and 45 (34.4%) had TB. For TB detection among HIV patients, sensitivity of MTB/RIF was 97.8% (95% CI 88.4–99.6) (44/45); specificity was 97.7% (95% CI 91.9–99.4) (84/86); the positive predictive value was 95.7% (95% CI 85.5–98.8) (44/46); and the negative predictive value, 98.8% (95% CI 93.6–99.8) (84/85). MTB/RIF detected 13/14 smear-negative TB cases, outperforming smear microscopy [97.8% (44/45) vs. 68.9% (31/45); p = 0.0002]. For rifampicin resistance detection, sensitivity of MTB/RIF was 100% (95% CI 61.0–100.0) (6/6); specificity was 91.0% (95% CI 76.4–96.9) (30/33); the positive predictive value was 66.7% (95% CI 35.4–87.9) (6/9); and the negative predictive value was 100% (95% CI 88.7 –100.0) (30/30).Conclusions/SignificanceIn HIV patients in our population with a high clinical suspicion of TB, MTB/RIF performed well for TB diagnosis and outperformed smear microscopy.