[Show abstract][Hide abstract] ABSTRACT: Interferon-γ release assays (IGRAs) are blood-based tests intended for diagnosis of latent tuberculosis infection (LTBI).
IGRAs offer logistical advantages and are supposed to offer improved specificity over the tuberculin skin test (TST). However,
recent serial testing studies in low risk individuals have revealed higher false conversion rates with IGRAs compared with
TST. Reproducibility studies have identified various sources of variability that contribute to non-reproducible results. Sources
of variability can be broadly classified as pre-analytical, analytical, post-analytical, manufacturing, and immunological.
In this review, we summarize known sources of variability and their impact on IGRA results. We also provide recommendations
on how to minimize sources of IGRA variability.
No preview · Article · Jan 2016 · Journal of clinical microbiology
[Show abstract][Hide abstract] ABSTRACT: Background:
Effective infectious disease control requires early diagnosis and treatment initiation. Point-of-care testing offers rapid turn-around-times, facilitating same day clinical management decisions. To maximize the benefits of such POC testing programs, we need to understand how rapid tests are used in everyday clinical practice.
In this cross-sectional survey study, 400 primary healthcare providers in two cities in South Africa were interviewed on their use of rapid tests in general, and tuberculosis diagnostic practices, between September 2012 and June 2013. Public healthcare facilities were selected using probability-sampling techniques and private healthcare providers were randomly selected from the Health Professional Council of South Africa list. To ascertain differences between the two healthcare sectors 2-sample z-tests were used to compare sample proportions.
The numbers of providers interviewed were equally distributed between the public (n = 200) and private sector (n = 200). The most frequently reported tests in the private sector include blood pressure (99.5%), glucose finger prick (89.5%) and urine dipstick (38.5%); and in the public sector were pregnancy (100%), urine dipstick (100%), blood pressure (100%), glucose finger prick (99%) and HIV rapid test (98%). The majority of TB testing occurs in the public sector, where significantly more providers prefer Xpert MTB/RIF assay, the designated clinical TB diagnostic tool by the national TB program, as compared to the private sector (87% versus 71%, p-value >0.0001). Challenges with regard to TB diagnosis included the long laboratory turn-around-time, difficulty in obtaining sputum samples and lost results. All providers indicated that a new POC test for TB should be rapid and cheap, have good sensitivity and specificity, ease of sample acquisition, detect drug-resistance and work in HIV-infected persons.
The existing centralized laboratory services, poor quality assurance, and lack of staff capacity deter the use of more rapid tests at POC. Further research into the practices and choices of these providers is necessary to aid the development of new POC tests.
[Show abstract][Hide abstract] ABSTRACT: Both product innovation (e.g., more sensitive tests) and process innovation (e.g., a point-of-care [POC] testing programme) could improve patient outcomes.
To study the respective contributions of product and process innovation in improving patient outcomes.
We implemented a POC programme using Xpert(®) MTB/RIF in an out-patient clinic of a tertiary care hospital in India. We measured the impact of process innovation by comparing time to diagnosis with routine testing vs. POC testing. We measured the impact of product innovation by comparing accuracy and time to diagnosis using smear microscopy vs. POC Xpert.
We enrolled 1012 patients over a 15-month period. Xpert had high accuracy, but the incremental value of one Xpert over two smears was only 6% (95%CI 3-12). Implementing Xpert as a routine laboratory test did not reduce the time to diagnosis compared to smear-based diagnosis. In contrast, the POC programme reduced the time to diagnosis by 5.5 days (95%CI 4.3-6.7), but required dedicated staff and substantial adaptation of clinic workflow.
Process innovation by way of a POC Xpert programme had a greater impact on time to diagnosis than the product per se, and can yield important improvements in patient care that are complementary to those achieved by introducing innovative technologies.
Full-text · Article · Sep 2015 · The International Journal of Tuberculosis and Lung Disease
[Show abstract][Hide abstract] ABSTRACT: Background:
Successful point-of-care testing, namely ensuring the completion of the test and treat cycle in the same encounter, has immense potential to reduce diagnostic and treatment delays, and impact patient outcomes. However, having rapid tests is not enough, as many barriers may prevent their successful implementation in point-of-care testing programs. Qualitative research on diagnostic practices may help identify such barriers across different points of care in health systems.
In this exploratory qualitative study, we conducted 78 semi-structured interviews and 13 focus group discussions in an urban and rural area of Karnataka, India, with healthcare providers (doctors, nurses, specialists, traditional healers, and informal providers), patients, community health workers, test manufacturers, laboratory technicians, program managers and policy-makers. Participants were purposively sampled to represent settings of hospitals, peripheral labs, clinics, communities and homes, in both the public and private sectors.
In the Indian context, the onus is on the patient to ensure successful point-of-care testing across homes, clinics, labs and hospitals, amidst uncoordinated providers with divergent and often competing practices, in settings lacking material, money and human resources. We identified three overarching themes affecting point-of-care testing: the main theme is 'relationships' among providers and between providers and patients, influenced by the cross-cutting theme of 'infrastructure'. Challenges with both result in 'modified practices' often favouring empirical (symptomatic) treatment over treatment guided by testing.
Even if tests can be conducted on the spot and infrastructure challenges have been resolved, relationships among providers and between patients and providers are crucial for successful point-of-care testing. Furthermore, these barriers do not act in isolation, but are interlinked and need to be examined as such. Also, a test alone has only limited power to overcome those difficulties. Test developers, policy-makers, healthcare providers and funders need to use these insights in overcoming barriers to point-of-care testing programs.
[Show abstract][Hide abstract] ABSTRACT: The successful cure of tuberculosis (TB) is dependent on adherence to treatment. Various factors influence adherence, however, few are easily modifiable. There are limited data regarding correlates of psychological distress and their association with non-adherence to anti-TB treatment.
In a trial of a new TB test, we measured psychological distress (K-10 score), TB-related health literacy, and morbidity (TBscore), prior to diagnosis in 1502 patients with symptoms of pulmonary TB recruited from clinics in Cape Town (n = 419), Harare (n = 400), Lusaka (n = 400), Durban (n = 200), and Mbeya (n = 83). Socioeconomic, demographic, and alcohol usage-related data were captured. Patients initiated on treatment had their DOTS cards reviewed at two-and six-months.
22 %(95 % CI: 20 %, 25 %) of patients had severe psychological distress (K-10 ≥ 30). In a multivariable linear regression model, increased K-10 score was independently associated with previous TB [estimate (95 % CI) 0.98(0.09-1.87); p = 0.0304], increased TBscore [1(0.80, 1.20); p <0.0001], and heavy alcohol use [3.08(1.26, 4.91); p = 0.0010], whereas male gender was protective [-1.47(-2.28, -0.62); p = 0.0007]. 26 % (95 % CI: 21 %, 32 %) of 261 patients with culture-confirmed TB were non-adherent. In a multivariable logistic regression model for non-adherence, reduced TBscore [OR (95 % CI) 0.639 (0.497, 0.797); p = 0.0001], health literacy score [0.798(0.696, 0.906); p = 0.0008], and increased K-10 [1.082(1.033, 1.137); p = 0.0012], and heavy alcohol usage [14.83(2.083, 122.9); p = 0.0002], were independently associated. Culture-positive patients with a K-10 score ≥ 30 were more-likely to be non-adherent (OR = 2.290(1.033-5.126); p = 0.0416].
Severe psychological distress is frequent amongst TB patients in Southern Africa. Targeted interventions to alleviate psychological distress, alcohol use, and improve health literacy in newly-diagnosed TB patients could reduce non-adherence to treatment.
[Show abstract][Hide abstract] ABSTRACT: Tuberculosis (TB) is a major public health threat. But worldwide, the majority of people with symptoms consistent with TB start their care seeking in the private or informal sector. These numbers are particularly high in Asia.
Public-private mix (PPM) efforts have been introduced to reach these individuals, as soon as possible, with quality-assured diagnosis and treatment. Systematic approaches have been designed to reach all provider types. However, PPM schemes struggle to manage the scale of a fragmented and under-regulated private sector.
Opportunities are arising to introduce more systemic, scalable, and innovative approaches, including social businesses, insurance-based initiatives, intermediary agencies, regulatory regimes, and provider consolidation, with a heavy emphasis on the use of new information technologies.
These approaches combine the previous work on TB private sector engagement with structural solutions that make health systems function for all patients, regardless of the disease or whether patients seek care in the public or the private sector.
[Show abstract][Hide abstract] ABSTRACT: The core objective of any point-of-care (POC) testing program is to ensure that testing will result in an actionable management decision (e.g. referral, confirmatory test, treatment), within the same clinical encounter (e.g. POC continuum). This can but does not have to involve rapid tests. Most studies on POC testing focus on one specific test and disease in a particular healthcare setting. This paper describes the actors, technologies and practices involved in diagnosing major diseases in five Indian settings – the home, community, clinics, peripheral laboratories and hospitals. The aim was to understand how tests are used and fit into the health system and with what implications for the POC continuum.
The paper reports on a qualitative study including 78 semi-structured interviews and 13 focus group discussions with doctors, nurses, patients, lab technicians, program officers and informal providers, conducted between January and June 2013 in rural and urban Karnataka, South India. Actors, diseases, tests and diagnostic processes were mapped for each of the five settings and analyzed with regard to whether and how POC continuums are being ensured.
Successful POC testing hardly occurs in any of the five settings. In hospitals and public clinics, most of the rapid tests are used in laboratories where either the single patient encounter advantage is not realized or the rapidity is compromised. Lab-based testing in a context of manpower and equipment shortages leads to delays. In smaller peripheral laboratories and private clinics with shorter turn-around-times, rapid tests are unavailable or too costly. Here providers find alternative measures to ensure the POC continuum. In the home setting, patients who can afford a test are not/do not feel empowered to use those devices.
These results show that there is much diagnostic delay that deters the POC continuum. Existing rapid tests are currently not translated into treatment decisions rapidly or are not available where they could ensure shorter turn-around times, thus undermining their full potential. To ensure the success of POC testing programs, test developers, decision-makers and funders need to account for such ground realities and overcome barriers to POC testing programs.
Full-text · Article · Jun 2015 · BMC Health Services Research
[Show abstract][Hide abstract] ABSTRACT: Accurate and timely diagnosis is the first step for initiating effective treatment for tuberculosis (TB) and interrupting transmission. Worldwide, nearly one third of all TB cases go undetected or unreported each year. The emergence of extensively drug-resistant TB, in addition to challenges in detecting TB among children and people living with HIV has created an urgent need for better technologies. In the past 5 years, Xpert MTB/RIF has proved to be pathfinder for improved diagnosis. However, gaps remain. Currently, there is no molecular replacement for sputum smear microscopy at the level of peripheral laboratories. There is no simple, non-sputum-based biomarker test that can detect all forms of TB at the primary care level. There is also a need to align emerging TB drug regimens with appropriate companion diagnostics. This review describes advances in non-molecular and molecular diagnostics and their potential to fill the gaps in TB case detection.
[Show abstract][Hide abstract] ABSTRACT: Background:
There is growing concern that interferon-γ release assays (IGRAs) are being used off-label for the diagnosis of active tuberculosis (TB) disease in many high-burden settings, including India, where the background prevalence of latent TB infection is high. We analyzed the costs and consequences of using IGRAs for the diagnosis of active TB in India from the perspective of the Indian TB control sector.
Methods and findings:
We constructed a decision analytic model to estimate the incremental cost and effectiveness of IGRAs for the diagnosis of active TB in India. We compared a reference scenario of clinical examination and non-microbiological tests against scenarios in which clinical diagnosis was augmented by the addition of either sputum smear microscopy, IGRA, or Xpert MTB/RIF. We examined costs (in 2013 US dollars) and consequences from the perspective of the Indian healthcare sector. Relative to sputum smear microscopy, use of IGRA for active TB resulted in 23,700 (95% uncertainty range, UR: 3,800 - 38,300) additional true-positive diagnoses, but at the expense of 315,700 (95% UR: 118,300 - 388,400) additional false-positive diagnoses and an incremental cost of US$49.3 million (95% UR: $34.9 - $58.0 million) (2.9 billion Indian Rupees). Relative to Xpert MTB/RIF (including the cost of treatment for drug resistant TB), use of IGRA led to 400 additional TB cases treated (95% UR: [-8,000] - 16,200), 370,600 (95% UR: 252,200 - 441,700) more false-positive diagnoses, 70,400 (95% UR: [-7,900] - 247,200) fewer disability-adjusted life years averted, and US$14.6 million (95%UR: [-$7.2] - $28.7 million) (854 million Indian Rupees) in additional costs.
Using IGRAs for diagnosis of active TB in a setting like India results in tremendous overtreatment of people without TB, and substantial incremental cost with little gain in health. These results support the policies by WHO and Standards for TB Care in India, which discourage the use of IGRAs for the diagnosis of active TB in India and similar settings.
[Show abstract][Hide abstract] ABSTRACT: While Indian studies have assessed care providers' knowledge and practices, there is no systematic review on the quality of tuberculosis (TB) care.
We searched multiple sources to identify studies (2000-2014) on providers' knowledge and practices. We used the International Standards for TB Care to benchmark quality of care.
Of the 47 studies included, 35 were questionnaire surveys and 12 used chart abstraction. None assessed actual practice using standardised patients. Heterogeneity in the findings precluded meta-analysis. Of 22 studies evaluating provider knowledge about using sputum smears for diagnosis, 10 found that less than half of providers had correct knowledge; 3 of 4 studies assessing self-reported practices by providers found that less than a quarter reported ordering smears for patients with chest symptoms. In 11 of 14 studies that assessed treatment, less than one third of providers knew the standard regimen for drug-susceptible TB. Adherence to standards in practice was generally lower than correct knowledge of those standards. Eleven studies with both public and private providers found higher levels of appropriate knowledge/practice in the public sector.
Available evidence suggests suboptimal quality of TB care, particularly in the private sector. Improvement of quality of care should be a priority for India.
Full-text · Article · Apr 2015 · The International Journal of Tuberculosis and Lung Disease