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Objective: To evaluate the implementation of new operational workflows for simultaneous screening of coronavirus disease 2019 (COVID-19) and tuberculosis at four high-volume COVID-19 testing centres located in tertiary hospitals in Mumbai, India. Methods: Each centre already offering antigen-detecting rapid diagnostic tests were equipped with a rapid molecular testing platform for COVID-19 and tuberculosis, sufficient laboratory staff, and reagents and consumables for screening. Using a verbal tuberculosis questionnaire, a patient follow-up agent screened individuals visiting the COVID-19 testing centres. Presumptive tuberculosis patients were asked to provide sputum samples for rapid molecular testing. Subsequently, we reversed our operational workflow to also screen patients visiting tuberculosis outpatient departments for COVID-19, using rapid diagnostic tests. Results: From March to December 2021, we screened 14 588 presumptive COVID-19 patients for tuberculosis, of whom 475 (3.3%) were identified as having presumptive tuberculosis. Of these, 288 (60.6%) were tested and 32 individuals (11.1%) were identified as tuberculosis positive (219 cases per 100 000 individuals screened). Of the tuberculosis-positive individuals, three had rifampicin-resistant tuberculosis. Among the remaining 187 presumptive tuberculosis cases not tested, 174 reported no symptoms at follow-up and 13 individuals either refused testing or could not be traced. Of the 671 presumptive tuberculosis cases screened for COVID-19, 17 (2.5%) were positive by antigen rapid diagnostic tests, and five (0.7%) who tested negative, later tested positive on the molecular testing platform (2483 COVID-19 cases per 100 000 individuals screened). Conclusion: Simultaneous screening for COVID-19 and tuberculosis in India is operationally feasible and can improve real-time on-site detection of COVID-19 and tuberculosis.
Subject(s)
COVID-19 , Mycobacterium tuberculosis , Tuberculosis, Multidrug-Resistant , Tuberculosis , Humans , COVID-19 Testing , COVID-19/diagnosis , COVID-19/epidemiology , Tuberculosis/diagnosis , Tuberculosis/epidemiology , India/epidemiology , Mass Screening , Sensitivity and Specificity , SputumABSTRACT
Objective: To describe the changes in tuberculosis case notifications by the private sector after implementation of the Joint Effort for Elimination of Tuberculosis project in India in 2018. Methods: We retrieved data from the project recorded in India's national tuberculosis surveillance system. We analysed data on 95 project districts in six states (Andhra Pradesh, Himachal Pradesh, Karnataka, Punjab including Chandigarh, Telangana and West Bengal) to assess changes in the number of tuberculosis notifications, private provider notifiers and microbiological confirmations of cases from 2017 (baseline) to 2019. We compared case notification rates in districts where the project was implemented with the rates in districts where it was not. Findings: From 2017 to 2019, tuberculosis notifications increased by 138.1% (from 44 695 to 106 404), and case notification rates more than doubled from 20 to 44 per 100 000 population. The number of private notifiers increased by over threefold, from 2912 to 9525, during this period. The number of microbiologically confirmed pulmonary and extra-pulmonary tuberculosis cases notified increased by more than two times (from 10 780 to 25 384) and nearly three times (from 1477 to 4096), respectively. The districts where the project was implemented showed a 150.3% increase in case notification rates per 100 000 population from 2017 to 2019 (from 16.8 to 41.9) while in non-project districts, this increase was only 89.8% (from 6.1 to 11.6). Conclusion: The substantial increase in tuberculosis notifications demonstrate the value of the project in engaging the private sector. Scaling up these interventions is important to consolidate and extend these gains towards tuberculosis elimination.
Subject(s)
Tuberculosis, Extrapulmonary , Tuberculosis , Humans , India/epidemiology , Tuberculosis/epidemiology , Tuberculosis/prevention & control , Private Sector , RecordsABSTRACT
BACKGROUND AND AIMS: India has a significant burden of hepatitis C virus (HCV) infection and has committed to achieving national elimination by 2030. This will require a substantial scale-up in testing and treatment. The "HEAD-Start Project Delhi" aimed to enhance HCV diagnosis and treatment pathways among the general population. METHODS: A prospective study was conducted at 5 district hospitals (Arm 1: one-stop shop), 15 polyclinics (Arm 2: referral for viral load (VL) testing and treatment) and 62 screening camps (Arm 3: referral for treatment). HCV prevalence, retention in the HCV care cascade, and turn-around time were measured. RESULTS: Between January and September 2019, 37 425 participants were screened for HCV. The median (IQR) age of participants was 35 (26-48) years, with 50.4% male and 49.6% female. A significantly higher proportion of participants in Arm 1 (93.7%) and Arm 3 (90.3%) received a VL test compared with Arm 2 (52.5%, P < .001). Of those confirmed positive, treatment was initiated at significantly higher rates for participants in both Arms 1 (85.6%) and 2 (73.7%) compared to Arm 3 (41.8%, P < .001). Arm 1 was found to be a cost-saving strategy compared to Arm 2, Arm 3, and no action. CONCLUSIONS: Delivery of all services at a single site (district hospitals) resulted in a higher yield of HCV seropositive cases and retention compared with sites where participants were referred elsewhere for VL testing and/or treatment. The highest level of retention in the care cascade was also associated with the shortest turn-around times.
Subject(s)
Hepacivirus , Hepatitis C , Adult , Feasibility Studies , Female , Hepatitis C/diagnosis , Hepatitis C/epidemiology , Hepatitis C/therapy , Humans , India/epidemiology , Male , Middle Aged , Prospective StudiesABSTRACT
BACKGROUND: Bringing reliable and accurate tuberculosis (TB) diagnosis closer to patients is a key priority for global TB control. Molbio Diagnostics have developed the Truenat point-of-care molecular assays for detection of TB and rifampicin (RIF) resistance. METHODS: We conducted a prospective multicentre diagnostic accuracy study at 19 primary healthcare centres and seven reference laboratories in Peru, India, Ethiopia and Papua New Guinea to estimate the diagnostic accuracy of the point-of-care Truenat MTB, MTB Plus and MTB-RIF Dx assays for pulmonary TB using culture and phenotypic drug susceptibility testing as the reference standard, compared with Xpert MTB/RIF or Ultra. RESULTS: Of 1807 enrolled participants with TB signs/symptoms, 24% were culture-positive for Mycobacterium tuberculosis, of which 15% were RIF-resistant. In microscopy centres, the pooled sensitivity of Truenat MTB and Truenat MTB Plus was 73% (95% CI 67-78%) and 80% (95% CI 75-84%), respectively. Among smear-negative specimens, sensitivities were 36% (95% CI 27-47%) and 47% (95% CI 37-58%), respectively. Sensitivity of Truenat MTB-RIF was 84% (95% CI 62-95%). Truenat assays showed high specificity. Head-to-head comparison in the central reference laboratories suggested that the Truenat assays have similar performance to Xpert MTB/RIF. CONCLUSION: We found the performance of Molbio's Truenat MTB, MTB Plus and MTB-RIF Dx assays to be comparable to that of the Xpert MTB/RIF assay. Performing the Truenat tests in primary healthcare centres with very limited infrastructure was feasible. These data supported the development of a World Health Organization policy recommendation of the Molbio assays.
Subject(s)
Antibiotics, Antitubercular , Mycobacterium tuberculosis , Tuberculosis , Antibiotics, Antitubercular/therapeutic use , Drug Resistance, Bacterial , Humans , Microbial Sensitivity Tests , Prospective Studies , Sensitivity and Specificity , Sputum , Tuberculosis/diagnosis , Tuberculosis/drug therapyABSTRACT
BACKGROUND: Acute febrile illness (AFI) is characterized by malaise, myalgia and a raised temperature that is a nonspecific manifestation of infectious diseases in the tropics. The lack of appropriate diagnostics for the evaluation of AFI leads to increased morbidity and mortality in resource-limited settings, specifically low-income countries like India. The review aimed to identify the number, type and quality of diagnostics used for AFI evaluation during passive case detection at health care centres in South India. METHODS: A scoping review of peer-reviewed English language original research articles published between 1946-July 2018 from four databases was undertaken to assess the type and number of diagnostics used in AFI evaluation in South India. Results were stratified according to types of pathogen-specific tests used in AFI management. RESULTS: The review included a total of 40 studies, all conducted in tertiary care centres (80% in private settings). The studies demonstrated the use of 5-22 tests per patient for the evaluation of AFI. Among 25 studies evaluating possible causes of AFI, 96% tested for malaria followed by 80% for dengue, 72% for scrub typhus, 68% for typhoid and 60% for leptospirosis identifying these as commonly suspected causes of AFI. 54% studies diagnosed malaria with smear microscopy while others diagnosed dengue, scrub typhus, typhoid and leptospirosis using antibody or antigen detection assays. 39% studies used the Weil-Felix test (WFT) for scrub typhus diagnosis and 82% studies used the Widal test for diagnosing typhoid. CONCLUSIONS: The review demonstrated the use of five or more pathogen-specific tests in evaluating AFI as well as described the widespread use of suboptimal tests like the WFT and Widal in fever evaluation. It identified the need for the development of better-quality tests for aetiological diagnosis and improved standardised testing guidelines for AFI.
Subject(s)
Communicable Diseases/diagnosis , Antibodies/blood , Antigens/analysis , Dengue/diagnosis , Humans , India , Leptospirosis/diagnosis , Malaria/diagnosis , Scrub Typhus/diagnosis , Tertiary Care CentersABSTRACT
Renal dysplasia, the leading cause of renal failure in children, is characterized by disrupted branching of the collecting ducts and primitive tubules, with an expansion of the stroma, yet a role for the renal stroma in the genesis of renal dysplasia is not known. Here, we demonstrate that expression of ß-catenin, a key transcriptional co-activator in renal development, is markedly increased in the expanded stroma in human dysplastic tissue. To understand its contribution to the genesis of renal dysplasia, we generated a mouse model that overexpresses ß-catenin specifically in stromal progenitors, termed ß-cat(GOF-S) . Histopathological analysis of ß-cat(GOF) (-S) mice revealed a marked expansion of fibroblast cells surrounding primitive ducts and tubules, similar to defects observed in human dysplastic kidneys. Characterization of the renal stroma in ß-cat(GOF) (-S) mice revealed altered stromal cell differentiation in the expanded renal stroma demonstrating that this is not renal stroma but instead a population of stroma-like cells. These cells overexpress ectopic Wnt4 and Bmp4, factors necessary for endothelial cell migration and blood vessel formation. Characterization of the renal vasculature demonstrated disrupted endothelial cell migration, organization, and vascular morphogenesis in ß-cat(GOF) (-S) mice. Analysis of human dysplastic tissue demonstrated a remarkably similar phenotype to that observed in our mouse model, including altered stromal cell differentiation, ectopic Wnt4 expression in the stroma-like cells, and disrupted endothelial cell migration and vessel formation. Our findings demonstrate that the overexpression of ß-catenin in stromal cells is sufficient to cause renal dysplasia. Further, the pathogenesis of renal dysplasia is one of disrupted stromal differentiation and vascular morphogenesis. Taken together, this study demonstrates for the first time the contribution of stromal ß-catenin overexpression to the genesis of renal dysplasia. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Subject(s)
Cell Differentiation , Kidney Tubules, Proximal/abnormalities , Urogenital Abnormalities/genetics , Vascular Remodeling , beta Catenin/genetics , Animals , Bone Morphogenetic Protein 4/genetics , Bone Morphogenetic Protein 4/metabolism , Disease Models, Animal , Endothelial Cells/metabolism , Endothelial Cells/pathology , Gene Expression , Humans , Kidney/metabolism , Kidney/pathology , Kidney Tubules, Proximal/metabolism , Kidney Tubules, Proximal/pathology , Mice , Mice, Transgenic , Phenotype , Signal Transduction , Stromal Cells/metabolism , Urogenital Abnormalities/metabolism , Urogenital Abnormalities/pathology , Wnt4 Protein/genetics , Wnt4 Protein/metabolism , beta Catenin/metabolismABSTRACT
CKD is a significant health concern with an underlying genetic component. Multiple genome-wide association studies (GWASs) strongly associated CKD with the shroom family member 3 (SHROOM3) gene, which encodes an actin-associated protein important in epithelial morphogenesis. However, the role of SHROOM3 in kidney development and function is virtually unknown. Studies in zebrafish and rat showed that alterations in Shroom3 can result in glomerular dysfunction. Furthermore, human SHROOM3 variants can induce impaired kidney function in animal models. Here, we examined the temporal and spatial expression of Shroom3 in the mammalian kidney. We detected Shroom3 expression in the condensing mesenchyme, Bowman's capsule, and developing and mature podocytes in mice. Shroom3 null (Shroom3Gt/Gt) mice showed marked glomerular abnormalities, including cystic and collapsing/degenerating glomeruli, and marked disruptions in podocyte arrangement and morphology. These podocyte-specific abnormalities are associated with altered Rho-kinase/myosin II signaling and loss of apically distributed actin. Additionally, Shroom3 heterozygous (Shroom3Gt/+) mice showed developmental irregularities that manifested as adult-onset glomerulosclerosis and proteinuria. Taken together, our results establish the significance of Shroom3 in mammalian kidney development and progression of kidney disease. Specifically, Shroom3 maintains normal podocyte architecture in mice via modulation of the actomyosin network, which is essential for podocyte function. Furthermore, our findings strongly support the GWASs that suggest a role for SHROOM3 in human kidney disease.
Subject(s)
Kidney/embryology , Microfilament Proteins/deficiency , Renal Insufficiency, Chronic/etiology , Animals , Genome-Wide Association Study , Mice , Microfilament Proteins/genetics , PodocytesABSTRACT
Renal dysplasia, a developmental disorder characterized by defective ureteric branching morphogenesis and nephrogenesis, ranks as one of the major causes of renal failure among the pediatric population. Herein, we demonstrate that the levels of activated ß-catenin are elevated in the nuclei of ureteric, stromal, and mesenchymal cells within dysplastic human kidney tissue. By using a conditional mouse model of mesenchymal ß-catenin overexpression, we identify two novel signaling pathways mediated by ß-catenin in the development of renal dysplasia. First, the overexpression of ß-catenin within the metanephric mesenchyme leads to ectopic and disorganized branching morphogenesis caused by ß-catenin directly binding Tcf/lef consensus binding sites in the Gdnf promoter and up-regulating Gdnf transcription. Second, ß-catenin overexpression in the metanephric mesenchyme leads to elevated levels of transcriptionally active ß-catenin in the ureteric epithelium. Interestingly, this increase of ß-catenin-mediated transcription results from a novel Ret/ß-catenin signaling pathway. Consistent with these findings, analysis of human dysplastic renal tissue demonstrates that undifferentiated mesenchymal cells expressing high levels of ß-catenin also express increased GDNF. Furthermore, dysplastic ureteric tubules that were surrounded by high levels of GDNF also exhibited increased levels of activated ß-catenin. Together, these data support a model in which the elevation of ß-catenin in the metanephric mesenchyme results in cell-autonomous and non-cell-autonomous events that lead to the genesis of renal dysplasia.
Subject(s)
Kidney Diseases/pathology , Kidney/abnormalities , Kidney/pathology , Mesoderm/metabolism , Mesoderm/pathology , beta Catenin/metabolism , Animals , Female , Gene Expression Regulation , Glial Cell Line-Derived Neurotrophic Factor/genetics , Glial Cell Line-Derived Neurotrophic Factor/metabolism , HEK293 Cells , Humans , Kidney/embryology , Kidney Diseases/metabolism , Male , Mice , Models, Biological , Morphogenesis , Mutation , Proto-Oncogene Proteins c-ret/metabolism , Signal Transduction , Transcription, Genetic , Wnt Proteins/metabolismABSTRACT
North-west Syria (NWS) is a conflict-affected and unstable area. Due to its limited health infrastructure, accessing advanced COVID-19 testing services is challenging. COVID-19 antigen rapid diagnostic tests (Ag-RDTs) have the potential to overcome this barrier. A pilot project was implemented to introduce Ag-RDTs in NWS, aiming to determine the feasibility, uptake, and results of Ag-RDTs and identify facilitators and barriers to testing with Ag-RDTs. A cross-sectional study design involving secondary analysis of data collected during the project was employed. A local non-governmental organization implemented 25,000 Ag-RDTs that were conducted cross-border by trained community health workers. In total, 27,888 eligible individuals were enrolled, 24,956 (89.5%) consented to test, and 121 (0.5%) were COVID-19-positive. The highest positivity was observed among those with severe COVID-19 symptoms (12.7%), with respiratory illnesses (2.5%), enrolled at hospitals in Afrin (2.5%), and healthcare workers (1.9%). A non-random sample of 236 individuals underwent confirmatory RT-PCR testing. Observed sensitivity, specificity, and positive and negative predictive values were 80.0%, 96.1%, 91.4%, and 90.3%, respectively. Challenges included obtaining informed consent and conducting confirmatory testing. Ag-RDTs represent a feasible screening/diagnostic tool for COVID-19 infections in NWS, with nearly 90% uptake. Embedding Ag-RDTs into COVID-19 testing and screening strategies would be highly beneficial.
ABSTRACT
BACKGROUND: Tata MD CHECK SARS-CoV-2 kit 1.0, a CRISPR based reverse transcription PCR (TMC-CRISPR) test was approved by Indian Council of Medical Research (ICMR) for COVID-19 diagnosis in India. To determine the potential for rapid roll-out of this test, we conducted performance characteristic and an operational feasibility assessment (OFA) at a tertiary care setting. INTERVENTION: The study was conducted at an ICMR approved COVID-19 RT-PCR laboratory of King Edward Memorial (KEM) hospital, Mumbai, India. The TMC-CRISPR test was evaluated against the gold-standard RT-PCR test using the same RNA sample extracted from fresh and frozen clinical specimens collected from COVID-19 suspects for routine diagnosis. TMC-CRISPR results were determined manually and using the Tata MD CHECK application. An independent agency conducted interviews of relevant laboratory staff and supervisors for OFA. RESULTS: Overall, 2,332 (fresh: 2,121, frozen: 211) clinical specimens were analysed of which, 140 (6%) were detected positive for COVID-19 by TMC-CRISPR compared to 261 (11%) by RT-PCR. Overall sensitivity and specificity of CRISPR was 44% (95% CI: 38.1%-50.1%) and 99% (95% CI: 98.2%-99.1%) respectively when compared to RT-PCR. Discordance between TMC-CRISPR and RT-PCR results increased with increasing Ct values and corresponding decreasing viral load (range: <20% to >85%). In the OFA, all participants indicated no additional requirements of training to set up RT PCR. However, extra post-PCR steps such as setting up the CRISPR reaction and handling of detection strips were time consuming and required special training. No significant difference was observed between manual and mobile app-based readings. However, issues such as erroneous results, difficulty in interpretation of faint bands, internet connectivity, data safety and security were highlighted as challenges with the app-based readings. CONCLUSION: The evaluated version-Tata MD CHECK SARS-CoV-2 kit 1.0 of TMC-CRISPR test cannot be considered as an alternative to the RT-PCR. There is a definite scope for improvement in this assay.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , COVID-19/diagnosis , COVID-19 Testing , Feasibility Studies , Diagnostic Tests, RoutineABSTRACT
Content available: Audio Recording.
ABSTRACT
A lack of laboratory capacity for drug-resistant tuberculosis (DR-TB) testing is a major barrier to DR-TB control. To overcome this barrier, the Central Tuberculosis Division (CTD), Ministry of Health and Family Welfare (MoHFW), Government of India (GoI), and FIND India established a partnership under the National Tuberculosis Elimination Program (NTEP) to strengthen and expand tuberculosis (TB) laboratory diagnostic capabilities. This partnership has led to the establishment of 61 culture & DST laboratories, increasing the testing capacity to a capability of performing over 200,000 liquid cultures and over 170,000 molecular drug sensitivity tests annually. In this study, we assess the data on throughput, efficiency, investment cost, and the capacity of the laboratory services supported by this partnership to understand impact and inform future resource allocation. We estimated the technical efficiency using Stochastic Frontier Analysis (SFA). Our results show that the established laboratory network is operating at 69% efficiency, with the capacity to perform an additional 450,000 cultures and 180,000 first-line molecular drug-susceptibility tests by 2025. This additional capacity, together with current efforts to enhance the laboratory network, has the potential to make a significant contribution to NTEP's TB elimination target by 2025.
Subject(s)
Mycobacterium tuberculosis , Tuberculosis, Multidrug-Resistant , Tuberculosis , Antitubercular Agents/pharmacology , Antitubercular Agents/therapeutic use , Humans , India/epidemiology , Laboratories , Microbial Sensitivity Tests , Tuberculosis/diagnosis , Tuberculosis/drug therapy , Tuberculosis/epidemiology , Tuberculosis, Multidrug-Resistant/diagnosis , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/epidemiologyABSTRACT
Background: India's dominant private healthcare sector is the destination for 60-85% of initial tuberculosis care-seeking. The COVID-19 pandemic in India drastically affected TB case notifications in the first half of 2020. In this survey, we assessed the impact of the first wave of COVID-19 in India on private providers, and changes they adopted in their practice due to the pandemic. Methods: The Joint Effort for Elimination of TB (JEET) is a nationwide Global Fund project implemented across 406 districts in 23 states to extend quality TB services to patients seeking care in private sector. We conducted a rapid survey of 11% (2,750) of active providers engaged under JEET's intense Patient Provider Support Agency (PPSA) model across 15 Indian states in Q1 (February-March) of 2021. Providers were contacted in person or telephonically, and consenting participants were interviewed using a web-based survey tool. Responses from participants were elicited on their practice before COVID-19, during the 2020 lockdowns (March-April 2020) and currently (Q1 2021). Data were adjusted for survey design and non-response, and results were summarised using descriptive statistics and logistic regression. Results: Of the 2,750 providers sampled, 2,011 consented and were surveyed (73 % response). Nearly 50 % were between 30 and 45 years of age, and 51 % were from Uttar Pradesh, Maharashtra and Gujarat. Seventy percent of providers reported reduced daily out-patient numbers in Q1 2021 compared to pre-COVID times. During the lockdown, 898 (40 %) of providers said their facilities were closed, while 323 (11 %) offered limited services including teleconsultation. In Q1 2021, 88 % of provider facilities were fully open, with 10 % providing adjusted services, and 4 % using teleconsultation. Only 2 % remained completely closed. Majority of the providers (92 %) reported not experiencing any delays in TB testing in Q1 2021 compared to pre-COVID times. Only 6 % reported raising costs at their clinic, mostly to cover personal protective equipment (PPE) and other infection control measures, although 60-90 % implemented various infection control measures. Thirty-three percent of TB providers were ordering COVID-19 testing, in addition to TB testing.To adapt, 82% of survey providers implemented social distancing and increased timing between appointments and 83% started conducting temperature checks, with variation by state and provider type, while 89% adopted additional sanitation measures in their facilities. Furthermore, 62% of providers started using PPE, and 13% made physical changes (air filters, isolation of patient areas) to their clinic to prevent infection. Seventy percent of providers stated that infection control measures could decrease TB transmission. Conclusion: Although COVID-19 restrictions resulted in significant declines in patient turn-out at private facilities, our analysis showed that most providers were open and costs for TB care remained mostly the same in Q1 2021. As result of the COVID-19 pandemic, several positive strategies have been adapted by the private sector TB care providers. Since the subsequent COVID-19 waves were more severe or widespread, additional work is needed to assess the impact of the pandemic on the private health sector.
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BACKGROUND: A significant proportion of pediatric tuberculosis (TB) patients go unnotified due to the challenges in diagnosis of TB among children. The experiences of this vulnerable group while going through the TB care cascade remain largely undocumented. The aim of this study was to explore the experiences of pediatric TB patients and families along the pathway to TB diagnosis and appropriate treatment in four cities of India. METHODS: The study used a mixed methods, single phased, embedded design. The primary qualitative and secondary quantitative data were collected simultaneously by interviewing families of 100 randomly selected Xpert MTB/RIF positive pediatric TB patients, under the pediatric TB project, in 4 Indian cities using a semi-structured questionnaire. The qualitative component was analyzed to deduce patterns and themes on the patient and family experiences. Descriptive statistics were used to quantify various events along the TB care pathway including various delays (patient, diagnosis and total) and number of providers visited by patients during the diagnostic process. RESULTS: The median patient, diagnostic and total delays were 3 (IQR: 2,5), 39 (IQR: 23, 91) and 43 days (IQR: 28.5, 98.5), respectively. Patients visited a median of 3 (IQR: 2,4) providers before accessing Xpert MTB/RIF testing. On an average, 68.4% of physicians ordered any test most of them being irrelevant for TB diagnosis. Qualitative data showed considerable suffering for children and their families before and after TB diagnosis including serious concerns of stigma, disruption in education and social life and recurrence of the disease. CONCLUSION: Our study highlights the significant physical and social distress that the children with TB and their families undergo along the TB care pathway. It also shows diagnostic delay in excess of a month during which multiple providers were met and the patients underwent several diagnostic tests, most of them being inappropriate. Efforts to make Xpert MTB/RIF testing more accessible and part of physicians' toolkit will be of considerable value to ease the complexity of TB diagnosis in children. In addition, communication strategy needs to be developed and implemented to generate awareness among general population around pediatric TB and its management.
Subject(s)
Communication Barriers , Delayed Diagnosis , Family Health , Health Knowledge, Attitudes, Practice , Social Stigma , Time-to-Treatment , Tuberculosis , Child , Child Health Services/organization & administration , Child Health Services/standards , Critical Pathways/organization & administration , Delayed Diagnosis/adverse effects , Delayed Diagnosis/prevention & control , Delayed Diagnosis/psychology , Diagnostic Techniques and Procedures/standards , Diagnostic Techniques and Procedures/statistics & numerical data , Education , Humans , India/epidemiology , Mycobacterium tuberculosis/genetics , Mycobacterium tuberculosis/isolation & purification , Parents , Surveys and Questionnaires , Time-to-Treatment/standards , Time-to-Treatment/statistics & numerical data , Tuberculosis/diagnosis , Tuberculosis/epidemiology , Tuberculosis/therapyABSTRACT
BACKGROUND: Line probe assay (LPA) is standard diagnostic tool to detect multidrug resistant tuberculosis. Noninterpretable (NI) results in LPA (complete missing or light wild-type 3 and 8 bands with no mutation band in rpoB gene region) poses a diagnostic challenge. METHODS: Sputum samples obtained between October 2016 and July 2017 at the Intermediate Reference Laboratory, All India Institute of Medical Sciences Hospital, New Delhi, India were screened. Smear-positive and smear-negative culturepositive specimens were subjected to LPA Genotype MTBDRplus Ver 2.0. Smear-negative with culture-negative and culture contamination were excluded. LPA NI samples were subjected to phenotypic drug susceptibility testing (pDST) using MGIT-960 and sequencing. RESULTS: A total of 1,614 sputum specimens were screened and 1,340 were included for the study (smear-positive [n=1,188] and smear-negative culture-positive [n=152]). LPA demonstrated 1,306 (97.5%) valid results with TUB (Mycobacterium tuberculosis) band, 24 (1.8%) NI, three (0.2%) valid results without TUB band, and seven (0.5%) invalid results. Among the NI results, 22 isolates (91.7%) were found to be rifampicin (RIF) resistant and two (8.3%) were RIF sensitive in the pDST. Sequencing revealed that rpoB mutations were noted in all 22 cases with RIF resistance, whereas the remaining two cases had wild-type strains. Of the 22 cases with rpoB mutations, the most frequent mutation was S531W (n=10, 45.5%), followed by S531F (n=6, 27.2%), L530P (n=2, 9.1%), A532V (n=2, 9.1%), and L533P (n=2, 9.1%). CONCLUSION: The present study showed that the results of the Genotype MTBDRplus assay were NI in a small proportion of isolates. pDST and rpoB sequencing were useful in elucidating the cause and clinical meaning of the NI results.
ABSTRACT
Microbiological diagnosis of extra-pulmonary tuberculosis (EPTB) has been one of the most difficult aspects of tuberculosis (TB) management. Availability of better imaging and diagnostic modalities has led to an increase in the number of diagnosed cases. The current upsurge in multidrug-resistant tuberculosis warrants routine testing of EPTB samples for resistance at baseline with shorter turn-around time. A total of 369 EPTB specimens were subjected to Ziehl-Neelsen (ZN) stain, liquid culture (LC) with phenotypic drug susceptibility testing, MTBDRplus V.2 and MTBDRsl V.2. The molecular categorisation of resistant specimens was further reconfirmed with sequencing. The sensitivity and specificity of MTBDRplus V.2 to detect Mycobacterium tuberculosis (MTB) when compared to ZN stain was 97.9% and 89.2%, respectively while it was 73.4% and 83.8%, respectively when compared to LC. Similarly, for MTBDRsl V.2, the sensitivity and specificity for detection of MTB when compared with ZN was 95.6% and 91.9%, respectively and 75% and 89.2%, respectively when compared to LC. In smear-positive specimens, 94% (141/150) and 86% (129/150) valid results were observed in MTBDRplus V.2 and MTBDRsl V.2, respectively. The utilisation of both MTBDRplus V.2 and MTBDRsl V.2 for the diagnosis of smear-positive EPTB specimens would be useful in programmatic management of TB in high-burden settings.
Subject(s)
DNA, Bacterial/analysis , Mycobacterium tuberculosis/genetics , Tuberculosis, Multidrug-Resistant/diagnosis , Adult , Antitubercular Agents/therapeutic use , Female , Genotype , Humans , India/epidemiology , Male , Molecular Diagnostic Techniques/methods , Morbidity , Mycobacterium tuberculosis/isolation & purification , Retrospective Studies , Tuberculosis, Multidrug-Resistant/epidemiology , Tuberculosis, Multidrug-Resistant/microbiologyABSTRACT
BACKGROUND: Diagnosis of TB in pediatric population poses several challenges. A novel initiative was implemented in several major cities of India aimed at providing upfront access to free-of-cost Xpert MTB/RIF to presumptive pediatric TB cases. This paper aims to describe the experience of implementing this large initiative and assess feasibility of the intervention in high TB burden settings. METHODS: Data were drawn from the pediatric TB project implemented in 10 major cities of India between April 2014 and March 2018. In each city, providers, both public and private, were engaged and linked with a high throughput Xpert MTB/RIF lab (established in that city) through rapid specimen transportation and electronic reporting system. Rates and proportions were estimated to describe the characteristics of this cohort. RESULTS: Of the total 94,415 presumptive pediatric TB cases tested in the project, 6,270 were diagnosed positive for MTB (6.6%) on Xpert MTB/RIF (vs 2% on smear microscopy). Among MTB positives, 545 cases were rifampicin resistant (8.7%). The median duration between collection of specimens and reporting of results was 0 days (same day) and >89% cases were initiated on treatment. Approximately 50% of the specimens tested were non-sputum. The number of providers/facilities engaged under the project increased >10-fold (from 124 in Q2'14 to 1416 in Q1'18). CONCLUSION: This project, which was one of the largest initiatives globally among pediatric population, demonstrated the feasibility of sustaining rapid and upfront access to free-of-cost Xpert MTB/RIF testing. The project underscores the efficiency of this rapid diagnostic assay in tackling several challenges in pediatric TB diagnosis, identifies opportunities for further interventions as well as brings to light scope for effective engagement with healthcare providers. The findings have facilitated a policy decision by National TB Programme mandating the use of Xpert MTB/RIF as a primary diagnostic tool for TB diagnosis in children, which is being scaled-up.
Subject(s)
Mycobacterium tuberculosis/isolation & purification , Tuberculosis/diagnosis , Adolescent , Antibiotics, Antitubercular/therapeutic use , Child , Child, Preschool , Female , Health Personnel , Humans , India/epidemiology , Infant , Male , Mass Screening , Molecular Diagnostic Techniques , Mycobacterium tuberculosis/drug effects , Rifampin/therapeutic use , Tuberculosis/drug therapy , Tuberculosis/epidemiologyABSTRACT
BACKGROUND: Outreach and promotion programs are essential to ensuring uptake of new public health interventions and guidelines. We assessed the costs and operation dynamics of outreach and promotion efforts for up front Xpert MTB/RIF (Xpert) testing for pediatric presumptive tuberculosis (TB) patients in four major Indian cities. METHODS: Xpert test costs were assessed as weighted average per-test costs based on the daily workload dynamics matched by test volume specific Xpert unit cost at each study site. Costs of outreach programs to recruit health providers to refer pediatric patients for Xpert testing were assessed as cost per referral for each quarter based on total program costs and referral data. All costs were assessed in the health service provider's perspective and expressed in 2015 USD. RESULTS: Weighted average per-test costs ranged from $14.71 to $17.81 at the four laboratories assessed. Differences between laboratories were associated with unused testing capacity and/or frequencies of overtime work to cope with increasing demand and same-day testing requirements. Outreach activities generated between 825 and 2,065 Xpert testing referrals on average each quarter across the four study sites, translating into $0.63 to $2.55 per patient referred. Overall outreach costs per referral decreased with time, stabilizing at an average cost of $1.10, and demonstrated a clear association with increased referrals. CONCLUSIONS: Xpert test and outreach program costs within and across study sites were mainly driven by the dynamics of Xpert testing demand resulting from the combined outreach activities. However, these increases in demand required considerable overtime work resulting in additional costs and operational challenges at the study laboratories. Therefore, careful laboratory operational adjustment should be evaluated at target areas in parallel to the anticipated demand from the Xpert referral outreach program scale-up in other Indian regions.
Subject(s)
Genetic Testing , Health Care Costs , Molecular Diagnostic Techniques , Tuberculosis/diagnosis , Tuberculosis/economics , Workload , Adolescent , Bacterial Typing Techniques/economics , Bacterial Typing Techniques/standards , Child , Child, Preschool , Diagnosis, Differential , Female , Genetic Testing/economics , Genetic Testing/methods , Genetic Testing/standards , Health Care Costs/statistics & numerical data , Health Planning Guidelines , Humans , India/epidemiology , Infant , Infant, Newborn , Male , Molecular Diagnostic Techniques/economics , Molecular Diagnostic Techniques/methods , Molecular Diagnostic Techniques/standards , Patient Care Team/economics , Patient Care Team/organization & administration , Patient Care Team/standards , Referral and Consultation/organization & administration , Referral and Consultation/standards , Tuberculosis/epidemiology , Workload/economics , Workload/statistics & numerical dataABSTRACT
Cardiac adiposity defined as increased epicardial adipose tissue and massive deposits of fat within the atrial septum (lipomatous hypertrophy) is seen in overweight persons and is associated with coronary artery disease (CAD), atrial arrhythmias, and increased risk of left ventricular free wall rupture after acute myocardial infarction. Unlike subcutaneous fat, epicardial fat is metabollically active and produces hormones, cytokines, and other vasoactive substances that work systemically or locally to alter vascular endothelial function and may be implicated in the pathogenesis of CAD. The aim of the study was to assess the feasibility of measuring epicardial fat volume (EFV) and identify its clinical correlates using (64-slice) multislice computed tomography (MSCT). A protocol was devised to measure EFV using MSCT in 151 adults (age 26 to 83 years, mean 51 +/- 12; 55% men). Cross-sectional tomographic cardiac slices (2.5-mm thick) from base to apex (range 28 to 40 per heart) were traced semiautomatically using an off-line workstation, and EFV was measured by assigning Hounsfield units ranging from -30 to -250 to fat. Coronary computed tomographic angiography was performed using a standard protocol. EFV ranged from 25 to 274 ml (mean 121 +/- 47), corresponding to 2.4% to 30.5% (mean 15 +/- 5%) of total cardiac volume and correlated with age, atrial septum thickness, body weight, and body mass index. Coronary calcium score was significantly higher in patients with EFV >100 ml (67 +/- 155 vs 216 +/- 639; p = 0.03), and a higher percentage of patients with increased EFV had CAD (46% vs 31%; p <0.05) or metabolic syndrome (44% vs 29%; p <0.05). In conclusion, quantification of EFV was feasible using MSCT. Large deposits of fat around the heart and within the atrial septum were associated with obesity, coronary calcium, metabolic syndrome, and CAD. Measurement of EFV may provide another useful noninvasive indicator of heightened risk of CAD in addition to calcium score and coronary angiography.
Subject(s)
Adipose Tissue/diagnostic imaging , Pericardium/diagnostic imaging , Tomography, X-Ray Computed/methods , Adult , Age Factors , Aged , Aged, 80 and over , Body Mass Index , Calcinosis/diagnostic imaging , Coronary Angiography , Coronary Artery Disease/diagnostic imaging , Feasibility Studies , Female , Humans , Hypertension/epidemiology , Male , Metabolic Syndrome/epidemiology , Middle Aged , Obesity/epidemiologyABSTRACT
Turcot's syndrome (glioma-polyposis) is a rare hereditary disorder characterized by association of colonic polyposis with primary tumors of the central nervous system. We report a case of a 27-year-old male diagnosed with Turcot's syndrome after an autopsy. The patient survived for more than two decades after his initial presentation with medulloblastoma at the age of five years. Such a long survival is exceptional in patients with this syndrome. Based on the genetic mutations, the patients with Turcot's syndrome are classified into adenomatous polyposis coli (APC) group or hereditary non-polyposis colon cancer (HNPCC) group. The article highlights the contrasting features of the two groups.