Three networks/projects involving 27 European countries were established to investigate the quality of second-line drug (SLD) susceptibility testing with conventional and molecular methods. 1. The “Baltic-Nordic TB-Laboratory Network” comprised 11 reference laboratories in the Baltic-Nordic States. They performed SLD testing in the first phase with a panel of 20 Mycobacterium tuberculosis strains. After several laboratories made technical changes a second panel of 10 strains with a higher proportion of resistant strains were tested. Although the concordance for Ofloxacin, Kanamycin, and Capreomycin was consistently high, the largest improvements in performance were achieved for the analysis of Ofloxacin resistant (from 88.9 to 95.0%), and Capreomycin resistant (from 71.0 to 88.9%) strains. 2. Within the FP7 TB PAN-NET project (EU Grant agreement 223681) a quality control panel to standardize the EQA (External Quality Assurance) for first-line drugs (FLD) and SLD testing for phenotypic and molecular methods was established. The strains were characterized by their robustness, unambiguous results when tested, and low proportion of secondary drug resistances. 3. The (European Reference Laboratory Network-TB) ERLN-TB network analyzed four different panels for drug resistance testing using phenotypic and molecular methods; in two rounds in 2010 the 31 participating laboratories began with 5 strains, followed by 10 strains and 6 additional crude DNA extracts in 2011 and 2012 were examined by conventional DST and molecular methods. Overall, we demonstrated the importance of developing inter-laboratory networks to establish quality assurance and improvement of SLD testing of M. tuberculosis.
Challenges exist regarding TB infection control and TB in hospital-based healthcare workers in South Africa. However, few studies report on TB in non-hospital based healthcare workers such as primary or community healthcare workers. Our objectives were to investigate the implementation of TB infection control measures at primary healthcare facilities, the smear positive TB incidence rate amongst primary healthcare workers and the association between TB infection control measures and all types of TB in healthcare workers.
One hundred and thirty three primary healthcare facilities were visited in five provinces of South Africa in 2009. At each facility, a TB infection control audit and facility questionnaire were completed. The number of healthcare workers who had had TB during the past three years was obtained.
The standardised incidence ratio of smear positive TB in primary healthcare workers indicated an incidence rate of more than double that of the general population. In a univariable logistic regression, the infection control audit score was significantly associated with reported cases of TB in healthcare workers (OR=1.04, 95%CI 1.01-1.08, p=0.02) as was the number of staff (OR=3.78, 95%CI 1.77-8.08). In the multivariable analysis, the number of staff remained significantly associated with TB in healthcare workers (OR=3.33, 95%CI 1.37-8.08).
The high rate of TB in healthcare workers suggests a substantial nosocomial transmission risk, but the infection control audit tool which was used did not perform adequately as a measure of this risk. Infection control measures should be monitored by validated tools developed and tested locally. Different strategies, such as routine surveillance systems, could be used to evaluate the burden of TB in healthcare workers in order to calculate TB incidence, monitor trends and implement interventions to decrease occupational TB.
Tobacco use leads to many health complications and is a risk factor for the occurrence of cardio vascular diseases, lung and oral cancers, chronic bronchitis etc. Almost 6 million people die from tobacco-related causes every year. This study was conducted to measure the prevalence of tobacco use in three different areas around Chennai city, south India.
A survey of 7510 individuals aged > = 15 years was undertaken covering Chennai city (urban), Ambattur (semi-urban) and Sriperumbudur (rural) taluk. Details on tobacco use were collected using a questionnaire adapted from both Global Youth Tobacco Survey and Global Adults Tobacco Survey.
The overall prevalence of tobacco use was significantly higher in the rural (23.7%) compared to semi-urban (20.9%) and urban (19.4%) areas (P value <0.001) Tobacco smoking prevalence was 14.3%, 13.9% and 12.4% in rural, semi-urban and urban areas respectively. The corresponding values for smokeless tobacco use were 9.5%, 7.0% and 7.0% respectively. Logistic regression analysis showed that the odds of using tobacco (with smoke or smokeless forms) was significantly higher among males, older individuals, alcoholics, in rural areas and slum localities. Behavioural pattern analysis of current tobacco users led to three groups (1) those who were not reached by family or friends to advice on harmful effects (2) those who were well aware of harmful effects of tobacco and even want to quit and (3) those are exposed to second hand/passive smoking at home and outside.
Tobacco use prevalence was significantly higher in rural areas, slum dwellers, males and older age groups in this region of south India. Women used mainly smokeless tobacco. Tobacco control programmes need to develop strategies to address the different subgroups among tobacco users. Public health facilities need to expand smoking cessation counseling services as well as provide pharmacotherapy where necessary.
Tuberculosis, reported as the second most common infectious cause of death worldwide, is a key mortality contributor in developing countries and globally. The disease is endemic in Peru and while relative success was achieved during the 1990s in its control, this slowed as new complications, such as multi drug resistant TB arose. Health centre workers participating in the national DOTS program, create the front-line TB work-force in Peru meaning their knowledge and attitudes about the disease are key in its control.
A Spanish language, multiple choice knowledge and attitudes survey was designed based on previous successful studies and the national Peruvian TB control guidelines. It was applied to two health networks in Lima, Peru amongst 301health workers participating in the national TB control program from 66 different health centres. The study results were analysed to test mean knowledge scores amongst different groups, overall gaps in key areas of TB treatment and control knowledge, and attitudes towards the disease and the national TB control program.
A mean knowledge score of 10.1 (+/- 1.7) out of 15 or 67.3% correct was shown. Demographics shown to have an effect on knowledge score were age and level of education. Major knowledge gaps were noted primarily in themes relating to treatment and diagnostics. Greater community involvement including better patient education about TB was seen as important in implementing the national TB control program. Participants were in disagreement about the current distribution of health resources throughout the study area.
Discussion Serious knowledge gaps were identified from the survey; these reflect findings from a previous study in Lima and other studies from TB endemic areas throughout the world. Understanding these gaps and observations made by front-line TB workers in Lima may help to improve the national TB control program and other control efforts globally.
Tuberculosis infection, disease and mortality are all less common at high than low altitude and ascent to high altitude was historically recommended for treatment. The immunological and mycobacterial mechanisms underlying the association between altitude and tuberculosis are unclear. We studied the effects of altitude on mycobacteria and antimycobacterial immunity.
Antimycobacterial immunity was assayed in 15 healthy adults residing at low altitude before and after they ascended to 3400 meters; and in 47 long-term high-altitude residents. Antimycobacterial immunity was assessed as the extent to which participants’ whole blood supported or restricted growth of genetically modified luminescent Bacille Calmette-Guérin (BCG) mycobacteria during 96 hours incubation. We developed a simplified whole blood assay that could be used by a technician in a low-technology setting. We used this to compare mycobacterial growth in participants’ whole blood versus positive-control culture broth and versus negative-control plasma.
Measurements of mycobacterial luminescence predicted the number of mycobacterial colonies cultured six weeks later. At low altitude, mycobacteria grew in blood at similar rates to positive-control culture broth whereas ascent to high altitude was associated with restriction (p≤0.002) of mycobacterial growth to be 4-times less than in culture broth. At low altitude, mycobacteria grew in blood 25-times more than negative-control plasma whereas ascent to high altitude was associated with restriction (p≤0.01) of mycobacterial growth to be only 6-times more than in plasma. There was no evidence of differences in antimycobacterial immunity at high altitude between people who had recently ascended to high altitude versus long-term high-altitude residents.
An assay of luminescent mycobacterial growth in whole blood was adapted and found to be feasible in low-resource settings. This demonstrated that ascent to or residence at high altitude was associated with decreased mycobacterial growth in whole blood relative to controls, consistent with altitude-related augmentation of antimycobacterial cellular immunity.
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.
HIV-infected prisoners at a single site provided two early-morning sputum specimens to be examined using fluorescence smear microscopy, BACTEC MGIT 960 liquid culture and a single Xpert. The sensitivity, specificity, negative and positive predictive values of Xpert were calculated relative to gold-standard results using MGIT 960 liquid culture. Relevant clinical and demographic data were used to examine correlates of active TB disease.
The majority of enrolled subjects with complete data (N=125) were men (90.4%), age <40 years (61.6%) and had injected drugs (75.2%). Median CD4 lymphocyte count was 337 cells/µL (IQR 149-492); only 19 (15.2%) were receiving antiretroviral therapy. Of 15 culture-positive TB cases, single Xpert assay accurately detected only eight previously undiagnosed TB cases, resulting in a sensitivity, specificity, positive predictive value and negative predictive value of 53.3% (95% CI 30.12-75.2%), 100% (95% CI 96.6-100%), 100% (95% CI 67.56-100%) and 94.0% (95% CI 88.2-97.1%), respectively. Only 1 of 15 (6.7%) active TB cases was smear-positive. The prevalence (12%) of undiagnosed active pulmonary TB (15 of 125 prisoners) was high and associated with longer duration of drug use (AOR 1.14, 95% CI 1.03-1.26, for each year of drug use).
Single Xpert assay improved TB case detection and outperformed AFB smear microscopy, but yielded low screening sensitivity. Further examination of the impact of HIV infection on the diagnostic performance of the new assay alongside other screening methods in correctional settings is warranted.
Private medical practitioners in Visakhapatnam district, Andhra Pradesh, India.
To evaluate self-reported TB diagnostic and treatment practices amongst private medical practitioners against benchmark practices articulated in the International Standards of Tuberculosis Care (ISTC), and factors associated with compliance with ISTC.
Cross- sectional survey using semi-structured interviews.
Of 296 randomly selected private practitioners, 201 (68%) were assessed for compliance to ISTC diagnostic and treatment standards in TB management. Only 11 (6%) followed a combination of 6 diagnostic standards together and only 1 followed a combination of all seven treatment standards together. There were 28 (14%) private practitioners who complied with a combination of three core ISTC (cough for tuberculosis suspects, sputum smear examination and use of standardized treatment). Higher ISTC compliance was associated with caring for more than 20 TB patients annually, prior sensitization to TB control guidelines, and practice of alternate systems of medicine.
Few private practitioners in Visakhapatnam, India reported TB diagnostic and treatment practices that met ISTC. Better engagement of the private sector is urgently required to improve TB management practices and to prevent diagnostic delay and drug resistance.
Twelve antiretroviral treatment centres under National AIDS Control Programme (NACP), Karnataka State, India.
For the period 2004-2011, to describe the trends in the numbers of people living with HIV (PLHIV) registered for care and their median baseline CD4 counts, disaggregated by age and sex.
Descriptive study involving analysis of routinely captured data (year of registration, age, sex, baseline CD4 count) under NACP.
34,882 (97% of total eligible) PLHIV were included in analysis. The number registered for care has increased by over 12 times during 2004-11; with increasing numbers among females. The median baseline CD4 cell count rose from 125 in 2004 to 235 in 2011 – the increase was greater among females as compared to males. However, about two-thirds still presented at CD4 cell counts less than 350.
We found an increasing trend of median CD4 counts among PLHIV presenting to ART centres in Karnataka, an indicator of enhanced and early access to HIV care. Equal proportion of females and higher baseline CD4 counts among them allays any fear of differential access by gender. Despite this relative success, a substantial proportion still presented at low CD4 cell counts indicating possibly delayed HIV diagnosis and delayed linkage to HIV care. Universal HIV testing at health care facilities and strengthening early access to care are required to bridge the gap.
Few studies have correlated the results of interferon (gamma interferon) release assays (IGRAs) with known markers of tuberculosis (TB) treatment response. We report the results of serial QuantiFERON-TB gold in-tube assay (QFT) testing on 149 patients with active tuberculosis and correlate the results with smear and culture conversion. We show that QFT results do not offer much value for treatment monitoring of TB disease.
The aims of the present study were to identify risk factors associated with latent tuberculosis (TB), examine the development of active disease among contacts, and assess the effectiveness of treating latent infection in indigenous Brazilians from January 2006 to December 2011. This was a retrospective study consisting of 1,371 tuberculosis contacts, 392 of whom underwent treatment for latent infection. Morbidity-from-TB data were obtained from the Information System for Disease Notification (SINAN) database, and the contacts’ data were collected from the clinical records using forms employed by Special Department of Indigenous Health (SESAI) multidisciplinary teams, according to SESAI’s instructions. The variables that were associated with latent infection among the contacts were age (odds ratio [OR]: 1.03; 95% confidence interval [CI]: 1.02–1.04) and close contact with a smear-positive index case (OR: 2.26, 95% CI: 1.59–3.22). The variables associated with the development of active TB among the contacts were a tuberculin skin test (TST) ≥10 mm (relative risk [RR]: 1.12, 95% CI: 1.07–1.17), age (RR: 1.01, 95% CI: 1.00–1.03), and treatment of latent infection (RR: 0.03, 95% CI: 0.01–0.27). The estimated number of latent infection treatments needed to prevent one case of active TB among the contacts was 51 treatments (95% CI: 33–182). In contacts with TST ≥10 mm, 10 (95% CI: 6–19) latent infection treatments were necessary to prevent one case of active TB. Age and close contact with a smear-positive index case were associated with latent TB. Screening with TST is a high priority among individuals contacting smear-positive index cases. Age and TST are associated with the development of active TB among contacts, and treatment of latent infection is an effective measure to control TB in indigenous communities.
Molecular genotyping methods have shown infection with more than one Mycobacterium tuberculosis strain genotype in a single sputum culture, indicating mixed infection.
This study aimed to develop a PCR-based genotyping tool to determine the population structure of M. tuberculosis strain genotypes in primary Mycobacterial Growth Indicator Tubes (MGIT) and Löwenstein–Jensen (LJ) cultures to identify mixed infections and to establish whether the growth media influenced the recovery of certain strain genotypes.
A convenience sample of 206 paired MGIT and LJ M. tuberculosis cultures from pulmonary tuberculosis patients resident in Khayelitsha, South Africa were genotyped using an in-house PCR-based method to detect defined M. tuberculosis strain genotypes.
The sensitivity and specificity of the PCR-based method for detecting Beijing, Haarlem, S-family, and LAM genotypes was 100%, and 75% and 50% for detecting the Low Copy Clade, respectively. Thirty-one (15%) of the 206 cases showed the presence of more than one M. tuberculosis strain genotype. Strains of the Beijing and Haarlem genotypes were significantly more associated with a mixed infection (on both media) when compared to infections with a single strain (Beijing MGIT p = 0.02; LJ, p<0.01) and (Haarlem: MGIT p<0.01; LJ, p = 0.01). Strains with the Beijing genotype were less likely to be with “other genotype” strains (p<0.01) while LAM, Haarlem, S-family and LCC occurred independently with the Beijing genotype.
The PCR-based method was able to identify mixed infection in at least 15% of the cases. LJ media was more sensitive in detecting mixed infections than MGIT media, implying that the growth characteristics of M. tuberculosis on different media may influence our ability to detect mixed infections. The Beijing and Haarlem genotypes were more likely to occur in a mixed infection than any of the other genotypes tested suggesting pathogen-pathogen compatibility.
Absence of a perfect reference test is an acknowledged source of bias in diagnostic studies. In the case of tuberculous pleuritis, standard reference tests such as smear microscopy, culture and biopsy have poor sensitivity. Yet meta-analyses of new tests for this disease have always assumed the reference standard is perfect, leading to biased estimates of the new test’s accuracy. We describe a method for joint meta-analysis of sensitivity and specificity of the diagnostic test under evaluation, while considering the imperfect nature of the reference standard. We use a Bayesian hierarchical model that takes into account within- and between-study variability. We show how to obtain pooled estimates of sensitivity and specificity, and how to plot a hierarchical summary receiver operating characteristic curve. We describe extensions of the model to situations where multiple reference tests are used, and where index and reference tests are conditionally dependent. The performance of the model is evaluated using simulations and illustrated using data from a meta-analysis of nucleic acid amplification tests (NAATs) for tuberculous pleuritis. The estimate of NAAT specificity was higher and the sensitivity lower compared to a model that assumed that the reference test was perfect.
PMID: 22568612 CAMSID: cams3174
Bayesian; Bivariate model; Diagnostic test accuracy; Latent class model; Meta-analysis
Pulmonary tuberculosis (TB) persists an important contributor to the burden of diseases in developing countries. TB control success is based on the patient’s compliance to the treatment. Depressive disorders have been negatively associated with compliance of therapeutic schemes for chronic diseases. This study aimed to estimate the significance and magnitude of major depressive episode as a hazard factor for negative outcomes (NO), including abandon or death in patients receiving TB treatment.
A longitudinal study was conducted to evaluate the association of major depressive episode (MDE), as measured by a 5-item version of the Center for Epidemiological Studies Depression Scale (CES-D) with NO to TB treatment. Patients with confirmed TB were enrolled before the start of TB treatment. Baseline measurements included socio-demographic variables as well as the CES-D, which was also applied every month until the end of the treatment. Death and treatment default were assessed monthly. Survivor function (SF) for NO according to MDE status (CES-D≥6) at baseline (MDEb) was estimated. Cox’s Regression was performed for bivariate analyses as well as for the multivariate model. A total of 325 patients accepted to participate in the study, of which 34 where excluded for diagnosis of MDR-TB. NO was observed in 24 patients (8.2%); 109 (37%) presented MDEb. Statistically significant difference was found on the SF of patients with and without MDEb (0.85 vs. 0.96, p-value = 0.002). The hazard ratio for NO, controlled for age, sex, marital status and instruction level was 3.54 (95%CI 1.43–8.75; p-value = 0.006).
The presence of MDE at baseline is associated to NO of TB treatment. Targeting detection and treatment of MDE may improve TB treatment outcomes.
Trust in health care has been intensely researched in resource rich settings. Some studies in resource poor settings suggest that the dimensions and determinants of trust are likely to be different.
This study was done as a qualitative exploration of the dimensions and determinants of trust in health care in Tamil Nadu, a state in south India to assess the differences from dimensions and determinants in resource rich settings.
The participants included people belonging to marginalized communities with poor access to health care services and living in conditions of resource deprivation. A total of thirty five in depth interviews were conducted. The interviews were summarized and transcribed and data were analyzed following thematic analysis and grounded theory approach.
The key dimensions of trust in health care identified during the interviews were perceived competence, assurance of treatment irrespective of ability to pay or at any time of the day, patients’ willingness to accept drawbacks in health care, loyalty to the physician and respect for the physician. Comfort with the physician and health facility, personal involvement of the doctor with the patient, behavior and approach of doctor, economic factors, and health awareness were identified as factors determining the levels of trust in health care.
The dimensions and determinants of trust in health care in resource poor settings are different from that in resource rich settings. There is a need to develop scales to measure trust in health care in resource poor settings using these specific dimensions and determinants.
From long instances, it is debatable whether three sputum specimens are required for the diagnosis of pulmonary tuberculosis (TB) or TB can be diagnosed effectively using two consecutive sputum specimens. This study was set out to evaluate the significance of examining multiple sputum specimens in diagnosis of TB.
We retrospectively reviewed the acid-fast bacillus (AFB) smear and culture results of three consecutive days’ sputum specimens from 413 confirmed TB patients which were detected as part of a larger active case finding study in Dhaka Central Jail, the largest correctional facility in Bangladesh.
AFB was detected from 81% (n = 334) patients, of which 89% (n = 297) were diagnosed from the first and additional 9% (n = 30) were from the second sputum specimen. M. tuberculosis growth was observed for 406 patients and 85% (n = 343) were obtained from the first sputum and additional 10% (n = 42) were from the second one. The third specimen didn’t show significant additional diagnostic value for the detection of AFB by microscopy or growth of the M. tuberculosis.
We concluded from our study results that examining two consecutive sputum specimens is sufficient enough for the effective diagnosis of TB. It can also decrease the laboratory workload and hence improve the quality of work in settings with high TB burden like Bangladesh.
In 2010, foreign-born persons accounted for 60% of all tuberculosis (TB) cases in the United States. Understanding which national groups make up the highest proportion of TB cases will assist TB control programs in concentrating limited resources where they can provide the greatest impact on preventing transmission of TB disease. The objective of our study was to predict through 2020 the numbers of U.S. TB cases among U.S.-born, foreign-born and foreign-born persons from selected countries of birth. TB case counts reported through the National Tuberculosis Surveillance System from 2000–2010 were log-transformed, and linear regression was performed to calculate predicted annual case counts and 95% prediction intervals for 2011–2020. Data were analyzed in 2011 before 2011 case counts were known. Decreases were predicted between 2010 observed and 2020 predicted counts for total TB cases (11,182 to 8,117 [95% prediction interval 7,262–9,073]) as well as TB cases among foreign-born persons from Mexico (1,541 to 1,420 [1,066–1,892]), the Philippines (740 to 724 [569–922]), India (578 to 553 [455–672]), Vietnam (532 to 429 [367–502]) and China (364 to 328 [249–433]). TB cases among persons who are U.S.-born and foreign-born were predicted to decline 47% (4,393 to 2,338 [2,113–2,586]) and 6% (6,720 to 6,343 [5,382–7,476]), respectively. Assuming rates of declines observed from 2000–2010 continue until 2020, a widening gap between the numbers of U.S.-born and foreign-born TB cases was predicted. TB case count predictions will help TB control programs identify needs for cultural competency, such as languages and interpreters needed for translating materials or engaging in appropriate community outreach.
Clinical laboratories are crucial in addressing the high rates of communicable and non-communicable diseases seen in sub-Saharan Africa (SSA). However, the most basic information, such as the number and quality of clinical laboratories in SSA, is not available. The objective of this study was to create a practical method for obtaining this information in SSA towns and cities using an initial survey in Kampala, Uganda.
Kampala city was divided into 5 partially-overlapping regions. Each region was assigned to 2–3 surveyors who identified and surveyed laboratories in their respective regions; in person and on foot. A modified version of the World Health Organization - African Region (WHO/AFRO) Laboratory Strengthening Checklist was used to obtain baseline measures of quality for all clinical laboratories within Kampala city. The surveyors also measured other attributes of each laboratory, such as their affiliation (government, private etc), designation (national hospital, district hospital, standalone etc), staff numbers, and type of staff.
The survey team identified and surveyed 954 laboratories in Kampala city. 96% of laboratories were private. Only 45 (5%) of the laboratories met or surpassed the lowest quality standards defined by the WHO/AFRO-derived laboratory strengthening tool (1-star). These 45 higher-quality laboratories were, on average, larger and had a higher number of laboratory-specific staff (technologists, phlebotomists etc) than the other 909 laboratories. 688 (72%) of the 954 laboratories were not registered with the Ministry of Health (MoH).
This comprehensive evaluation of the number, scope, and quality of clinical laboratories in Kampala is the first published survey of its kind in sub-Saharan Africa. The survey findings demonstrated that laboratories in Kampala that had qualified personnel and those that had higher testing volumes, tended to be of higher-quality.
As the South African province of KwaZulu-Natal addresses a growing multidrug-resistant tuberculosis (MDR-TB) epidemic by shifting care and treatment from trained specialty centers to community hospitals, delivering and monitoring MDR-TB therapy has presented new challenges. In particular, tracking and reporting adverse clinical events have been difficult for mobile healthcare workers (HCWs), trained health professionals who travel daily to patient homes to administer and monitor therapy. We designed and piloted a mobile phone application (Mobilize) for mobile HCWs that electronically standardized the recording and tracking of MDR-TB patients on low-cost, functional phones.
We assess the acceptability and feasibility of using Mobilize to record and submit adverse events forms weekly during the intensive phase of MDR-TB therapy and evaluate mobile HCW perceptions throughout the pilot period.
All five mobile HCWs at one site were trained and provided with phones. Utilizing a mixed-methods evaluation, mobile HCWs’ usage patterns were tracked electronically for seven months and analyzed. Qualitative focus groups and questionnaires were designed to understand the impact of mobile phone technology on the work environment.
Mobile HCWs submitted nine of 33 (27%) expected adverse events forms, conflicting with qualitative results in which mobile HCWs stated that Mobilize improved adverse events communication, helped their daily workflow, and could be successfully expanded to other health interventions. When presented with the conflict between their expressed views and actual practice, mobile HCWs cited forgetfulness and believed patients should take more responsibility for their own care.
This pilot experience demonstrated poor uptake by HCWs despite positive responses to using mHealth. Though our results should be interpreted cautiously because of the small number of mobile HCWs and MDR-TB patients in this study, we recommend carefully exploring the motivations of HCWs and technologic enhancements prior to scaling new mHealth initiatives in resource poor settings.
TB Control Programmes rely on passive case-finding to detect cases. TB notification remains low in Ethiopia despite major expansion of health services. Poor rural communities face many barriers to service access.
Methods and Findings
A community-based intervention package was implemented in Sidama zone, Ethiopia. The package included advocacy, training, engaging stakeholders and communities and active case-finding by female Health Extension Workers (HEWs) at village level. HEWs conducted house-to-house visits, identified individuals with a cough for two or more weeks, with or without other symptoms, collected sputum, prepared smears and supervised treatment. Supervisors transported smears for microscopy, started treatment, screened contacts and initiated Isoniazid preventive therapy (IPT) for children. Outcomes were compared with the pre-implementation period and a control zone. Qualitative research was conducted to understand community and provider perceptions and experiences.
HEWs screened 49,857 symptomatic individuals (60% women) from October 2010 to December 2011. 2,262 (4·5%) had smear-positive TB (53% women). Case notification increased from 64 to 127/100,000 population/year resulting in 5,090 PTB+ and 7,071 cases of all forms of TB. Of 8,005 contacts visited, 1,949 were symptomatic, 1,290 symptomatic were tested and 69 diagnosed with TB. 1,080 children received IPT. Treatment success for smear-positive TB increased from 77% to 93% and treatment default decreased from 11% to 3%. Service users and providers found the intervention package highly acceptable.
Community-based interventions made TB diagnostic and treatment services more accessible to the poor, women, elderly and children, doubling the notification rate and improving treatment outcome. This approach could improve TB diagnosis and treatment in other high burden settings.
To evaluate the prevalence of and factors associated with latent tuberculosis infection (LTBI) based on the tuberculin skin test (TST) and to estimate the boosted reaction rate among newly employed healthcare workers (HCWs).
Newly employed HCWs between January 2010 and July 2012 at Severance Hospital in South Korea were enrolled in this study. A one-step TST was conducted before October 2011, and a two-step TST after October 2011.
Of 2132 participants, 778 (36.5%) had positive TST results. Being older (odds ratio [OR] 1.10, 95% confidence interval [CI] 1.06–1.13, P<0.001), male (OR 1.78, 95% CI 1.21–2.62, P = 0.003), rejoining the hospital workforce (OR 1.58, 95% CI 1.04–2.40, P = 0.032), and having a previous history of tuberculosis (TB) (OR 18.21, 95% CI 2.15–154.10, P = 0.008) during the one-step period, and being older (OR 1.15, 95% CI 1.10–1.21, P<0.001) during the two-step period were significantly associated with a positive TST. A two-step TST was performed in 556 HCWs, and a boosted reaction was observed in 79 (14.2%). The induration size on the first TST (5–9-mm group) was the only factor associated with a boosted reaction on the second TST.
The prevalence of LTBI based on the TST among newly employed HCWs was high. The boosted reaction rate on two-step TST was not low; therefore, the use of two-step TST may be necessary for regular monitoring in countries with an intermediate TB burden and a high rate of Bacillus Calmette-Guérin vaccination.
One third of the world’s population is estimated to be latently infected with Mycobacterium tuberculosis (LTBI). Surveys of LTBI are rarely performed in resource poor TB high endemic countries like Tanzania although low-income countries harbor the largest burden of the worlds LTBI. The primary objective was to estimate the prevalence of LTBI in household contacts of pulmonary TB cases and a group of apparently healthy neighborhood controls in an urban setting of such a country. Secondly we assessed potential impact of LTBI on inflammation by quantitating circulating levels of an acute phase reactant: alpha-1-acid glycoprotein (AGP) in neighborhood controls.
The study was nested within the framework of two nutrition studies among TB patients in Mwanza, Tanzania. Household contacts- and neighborhood controls were invited to participate. The study involved a questionnaire, BMI determination and blood samples to measure AGP, HIV testing and a Quantiferon Gold In tube (QFN-IT) test to detect signs of LTBI.
245 household contacts and 192 neighborhood controls had available QFN-IT data. Among household contacts, the proportion of QFT-IT positive was 59% compared to 41% in the neighborhood controls (p = 0.001). In a linear regression model adjusted for sex, age, CD4 and HIV, a QFT-IT positive test was associated with a 10% higher level of alpha-1-acid glycoprotein(AGP) (10B 1.10, 95% CI 1.01; 1.20, p = 0.03), compared to individuals with a QFT-IT negative test.
LTBI is highly prevalent among apparently healthy urban Tanzanians even without known exposure to TB in the household. LTBI was found to be associated with elevated levels of AGP. The implications of this observation merit further studies.
The diagnosis of childhood tuberculosis (TB) disease remains a challenge especially in young and HIV-infected children. Recent studies have identified potential host markers which, when measured in Quantiferon (QFT-IT) supernatants, show promise in discriminating between Mycobacterium tuberculosis (M.tb) infection states. In this study, the utility of such markers was investigated in children screened for TB in a setting with high TB incidence.
Methodology and Principal Findings
76 children (29% HIV-infected) with or without active TB provided blood specimens collected directly into QFT-IT tubes. After overnight incubation, culture supernatants were harvested, aliquoted and frozen for future immunological research purposes. Subsequently, the levels of 12 host markers previously identified as potential TB diagnostic markers were evaluated in these supernatants for their ability to discriminate between M.tb infection and disease states using the Luminex platform. Of the 76 children included, 19 (25%) had culture confirmed TB disease; 26 (46%) of the 57 without TB had positive markers of M.tb infection defined by a positive QFT-IT test. The potentially most useful analytes for diagnosing TB disease included IFN-α2, IL-1Ra, sCD40L and VEGF and the most useful markers for discriminating between QFT-IT positive children as TB or latent infection included IL-1Ra, IP-10 and VEGF. When markers were used in combinations of four, 84% of all children were accurately classified into their respective groups (TB disease or no TB), after leave-one-out cross validation.
Measurement of the levels of IFN-α2, IL-1Ra, sCD40L, IP-10 and VEGF in QFT-IT supernatants may be a useful method for diagnosing TB disease and differentiating between active TB disease and M.tb infection in children. Our observations warrant further investigation in larger well-characterized clinical cohorts.
Mycobacterium tuberculosis (MTB) persistently infects and survives within the host macrophages. Substantial genotypic variation exists among MTB strains which correlate with their interactions with the host. The present study was designed to establish a correlation, if any, between infection and induction of innate immune response by genetically diverse drug resistant MTB isolates from India. For this purpose, three clinical isolates from ancient and modern lineages, along with H37Ra and H37Rv were evaluated for intracellular growth, phagocytic index, induction of proinflammatory cytokines and apoptosis following infection in THP-1 cell line. A wide variation in the induction of cytokines was revealed subsequent to infection with different strains. EAI-5 strain from ancient lineage 1, induced higher proinflammatory responses, higher apoptosis and moderate intracellular growth compared to other strains, in contrast, for Beijing strain of modern lineage 2, all three parameters were lowest among the clinical isolates. Further, the responses induced by LAM-6 from modern lineage 4 were at a moderate level, similar to the laboratory strain H37Rv which also belongs to lineage 4. Thus, these profiles were specific to their respective lineages and/or genotypes and independent of their drug resistance status. Further, a positive correlation, among TNF-α, IL-1β, IL-6 and IL-12 induced in infected THP-1 cells was demonstrated. In addition, induction of all pro-inflammatory cytokines correlated well with the host cell apoptosis. A positive correlation was observed between phagocytic index in the category of ‘>10 bacilli/cell’ and induction of apoptosis, only for virulent strains, indicating that initial accumulation of MTB strains inside the host cell may be an important determining factor for different innate responses.
Fluorescence microscopy (FM) has not been implemented widely in TB endemic settings and little evaluation has been done in HIV-infected patients. We evaluated diagnostic performance, time and costs of FM with light-emitting diodes technology (LED-FM), compared with conventional (Zieh-Neelsen) microscopy in a hospital in Indonesia which acts as referral centre for HIV-infected patients.
We included pulmonary tuberculosis suspects from the outpatient and HIV clinic. Direct and concentrated sputum smears were examined using LED-FM and ZN microscopy by two technicians who were blinded for the HIV-status and the result of the comparative test. Mean reading time per slide was recorded and cost of each slide was calculated. Mycobacteria culture served as the reference standard.
Among 404 tuberculosis suspects from the outpatient clinic and 256 from the HIV clinic, mycobacteria culture was positive in 12.6% and 27%, respectively. The optimal sensitivity of LED-FM was achieved by using a threshold of ≥2 AFB/length. LED-FM had a higher sensitivity (75.5% vs. 54.9%, P<0.01) but lower specificity (90.0% vs 96.6%, P<0.01) compared to ZN microscopy. HIV was associated with a lower sensitivity but similar specificity. The average reading time using LED-FM was significantly shorter (2.23±0.78 vs 5.82±1.60 minutes, P<0.01), while costs per slide were similar.
High sensitivity of LED-FM combined with shorter reading time of sputum smear slides make this method a potential alternative to ZN microscopy. Additional data on specificity are needed for effective implementation of this technique in high burden TB laboratories.
Globally treatment outcomes for multidrug-resistant Mycobacterium tuberculosis (MDR-TB) remain poor and this is compounded by high drug toxicity. Little is known about the influence of adverse drug reactions (ADRs) on treatment outcomes in South Africa.
We evaluated the impact of severe ADRs among a prospective cohort of MDR-TB patients in South Africa (2000–2004). The HIV-infected study participants were anti-retroviral naïve.
Of 2,079 patients enrolled, 1,390 (66.8%) were included in this analysis based on known HIV test results (39.1% HIV-infected). At least one severe ADR was reported in 83 (6.9%) patients with ototoxicity being the most frequent ADR experienced (38.9%).
We found that being HIV-infected but antiretroviral naïve did not increase occurrence of SADRs in patients on second-line anti-tuberculosis drugs. Early screening and proactive management of ADRs in this patient population is essential, especially given the rollout of decentralized care and the potential for overlapping toxicity of concomitant MDR-TB and HIV treatment.