Optimizing diagnostic networks to increase patient access to TB diagnostic services: Development of the diagnostic network optimization (DNO) approach and learnings from its application in Kenya, India and the Philippines.

Diagnostic network optimization (DNO) is an analytical approach that enables use of available country data to inform evidence-based decision-making to optimize access to diagnostic services. A DNO methodology was developed using available data sources and a commercial supply chain optimization software. In collaboration with Ministries of Health and partners, the approach was applied in Kenya, India and the Philippines to map TB diagnostic networks, identify misalignments, and determine optimal network design to increase patient access to TB diagnostic services and improve device utilization. The DNO analysis was successfully applied to evaluate and inform TB diagnostic services in Kenya, India and the Philippines as part of national strategic planning for TB. The analysis was tailored to each country's specific objectives and allowed evaluation of factors such as the number and placement of different TB diagnostics, design of sample referral networks and integration of early infant diagnosis for HIV at national and sub-national levels and across public and private sectors. Our work demonstrates the value of DNO as an innovative approach to analysing and modelling diagnostic networks, particularly suited for use in low-resource settings, as an open-access approach that can be applied to optimize networks for any disease.

Performance characteristics and operational feasibility assessment of a CRISPR based tata MD CHECK diagnostic test for SARS-CoV-2 (COVID-19).

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.

Simultaneous screening for COVID-19 and tuberculosis, India.

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.

Implementation of a tuberculosis elimination project, India 2018-2019.

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.

Strengthening resistance testing for tuberculosis in India - Investment cost, throughput, and efficiency of new laboratories.

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.

Adaptations to the first wave of the COVID-19 pandemic by private sector tuberculosis care providers in India.

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.

Pre-conference workshop on drug resistant TB - NATCON 2020.

Pre-conference workshop on Drug Resistant Tuberculosis was conducted under the banner of NATCON-2020 on 18th December 2020. The workshop covered various aspects of diagnosis including newer rapid genotypic methods, and gene sequencing. The workshop deliberated on the latest recommendations of the global and national guidelines about the management of DR-TB patients. Case scenarios focusing on the management of MDR TB and XDR TB patients were presented and the principles of making the regimen for DR-TB patients were discussed. Various aspects of shorter MDR TB regimen including bedaquiline containing shorter regimen and all oral longer regimen for DR-TB patients were also presented to the participants. The participants were also informed regarding what is in store in the near future at global and national level regarding the management of DR-TB patients. The participants included students, teaching faculty and the practicing physicians. The workshop informed the delegates on the latest recommendations of the global and national guidelines about the management of DR-TB. The detailed deliberations were very useful for the participants in their day-to-day clinical practice. The main highlights of the workshop have been mentioned below.

One year of COVID-19 and its impact on private provider engagement for TB: A rapid assessment of intermediary NGOs in seven high TB burden countries.

The COVID-19 pandemic has impacted health systems and health programs across the world. For tuberculosis (TB), it is predicted to set back progress by at least twelve years. Public private mix (PPM)has made a vital contribution to reach End TB targets with a ten-fold rise in TB notifications from private providers between 2012 and 2019. This is due in large part to the efforts of intermediary agencies, which aggregate demand from private providers. The COVID-19 pandemic has put these gains at risk over the past year. In this rapid assessment, representatives of 15 intermediary agencies from seven countries that are considered the highest priority for PPM in TB care (the Big Seven) share their views on the impact of COVID-19 on their programs, the private providers operating under their PPM schemes, and their private TB clients. All intermediaries reported a drop in TB testing and notifications, and the closure of some private practices. While travel restrictions and the fear of contracting COVID-19 were the main contributing factors, there were also unanticipated expenses for private providers, which were transferred to patients via increased prices. Intermediaries also had their routine activities disrupted and had to shift tasks and budgets to meet the new needs. However, the intermediaries and their partners rapidly adapted, including an increased use of digital tools, patient-centric services, and ancillary support for private providers. Despite many setbacks, the COVID-19 pandemic has underlined the importance of effective private sector engagement. The robust approach to fight COVID-19 has shown the possibilities for ending TB with a similar approach, augmented by the digital revolution around treatment and diagnostics and the push to decentralize health services.

Situational analysis of 10 countries with a high burden of drug-resistant tuberculosis 2 years post-UNHLM declaration: progress and setbacks in a changing landscape.

OBJECTIVES: Globally, drug-resistant tuberculosis (DR-TB) is the leading cause of death globally related to antimicrobial resistance, affecting 500,000 emergent cases annually. In 2018, the first United Nations High-Level Meeting (UNHLM) on tuberculosis declared DR-TB a global public health priority. Bold country targets were established for 2018-2022. This study reviews the DR-TB situation in 2018, and the UNHLM target accomplishments in 10 high-burden countries (HBCs). METHODS: An ecological descriptive analysis of the top 10 DR-TB HBCs (Bangladesh, China, India, Indonesia, Myanmar, Nigeria, Pakistan, Philippines, Russian Federation, and South Africa), which share 70% of the global DR-TB burden, was undertaken, complemented by a cascade-of-care analysis and a survey gathering additional information on key advances and setbacks 2 years after the UNHLM declaration. RESULTS: Most countries are showing historic advances and are on track for the 2018 and 2019 targets. However, according to the cascade-of-care, none of the countries are capable of providing effective care for 50% of the estimated patients. Increasing levels of fluoroquinolone resistance and access to timely susceptibility testing can jeopardize ongoing adoption of shorter, all-oral treatment regimens. The programmatic management of DR-TB in children remains minimal. Achievements for 2020 and beyond may be affected significantly by the coronavirus disease 2019 (COVID-19) pandemic. CONCLUSION: Triggered by the COVID-19 pandemic, there is a global risk of recoil in DR-TB care with long-term consequences in terms of deaths, suffering and wider transmission. Investment to support DR-TB services is more important now than ever to meet the aspirations of the UNHLM declaration.

Pathways to diagnosis of pediatric TB patients: A mixed methods study from India.

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.

A prospective multicentre diagnostic accuracy study for the Truenat tuberculosis assays.

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.

Impact of a package of diagnostic tools, clinical algorithm, and training and communication on outpatient acute fever case management in low- and middle-income countries: protocol for a randomized controlled trial.

BACKGROUND: The management of acute febrile illnesses places a heavy burden on clinical services in many low- and middle-income countries (LMICs). Bacterial and viral aetiologies of acute fevers are often clinically indistinguishable and, in the absence of diagnostic tests, the 'just-in-case' use of antibiotics by many health workers has become common practice, which has an impact on drug-resistant infections. Our study aims to answer the following question: in patients with undifferentiated febrile illness presenting to outpatient clinics/peripheral health centres in LMICs, can we demonstrate an improvement in clinical outcomes and reduce unnecessary antibiotic prescription over current practice by using a combination of simple, accurate diagnostic tests, clinical algorithms, and training and communication (intervention package)? METHODS: We designed a randomized, controlled clinical trial to evaluate the impact of our intervention package on clinical outcomes and antibiotic prescription rates in acute febrile illnesses. Available, point-of-care, pathogen-specific and non-pathogen specific (host markers), rapid diagnostic tests (RDTs) included in the intervention package were selected based on pre-defined criteria. Nine clinical study sites in six countries (Burkina Faso, Ghana, India, Myanmar, Nepal and Uganda), which represent heterogeneous outpatient care settings, were selected. We considered the expected seasonal variations in the incidence of acute febrile illnesses across all the sites by ensuring a recruitment period of 12 months. A master protocol was developed and adapted for country-specific ethical submissions. Diagnostic algorithms and choice of RDTs acknowledged current data on aetiologies of acute febrile illnesses in each country. We included a qualitative evaluation of drivers and/or deterrents of uptake of new diagnostics and antibiotic use for acute febrile illnesses. Sample size estimations were based on historical site data of antibiotic prescription practices for malarial and non-malarial acute fevers. Overall, 9 semi-independent studies will enrol a minimum of 21,876 patients and an aggregate data meta-analysis will be conducted on completion. DISCUSSION: This study is expected to generate vital evidence needed to inform policy decisions on the role of rapid diagnostic tests in the clinical management of acute febrile illnesses, with a view to controlling the rise of antimicrobial resistance in LMICs. TRIAL REGISTRATION: Clinicaltrials.gov NCT04081051 . Registered on 6 September 2019. Protocol version 1.4 dated 20 December 2019.

Upfront Xpert MTB/RIF for diagnosis of pediatric TB-Does it work? Experience from India.

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.

"Is there a difference in treatment outcome of tuberculosis patients: Rural Healthcare Providers versus Community Health Workers?"

INTRODUCTION: Rural healthcare providers (RHCPs) are the first point of contact for majority of patients in rural parts of India. A total of 75 RHCPs were trained and engaged in Hazaribagh to identify presumptive tuberculosis (TB) patients (PrTBPs) and refer them for diagnosis. Patients diagnosed with TB were initiated on directly observed treatment short course (DOTS) under the programme. Based on patients' choice, the treatment providers were either RHCPs or community health workers (CHWs). In this paper, we aim to compare the treatment outcomes of TB patients who received DOTS from RHCPs with CHWs. METHOD: This is a retrospective cohort study using secondary data routinely collected through project and Revised National TB Control Programme. RESULTS: Over the period of 24 months, 57 RHCPs continued to be engaged with project and a total of 382 referrals were made out of which 72 (19%) were diagnosed with TB. Based on choice made, 40 (55%) of TB patients chose RHCPs and 32 (45%) CHWs as their treatment provider. The mean successful treatment completion rate was 87% in the RHCP group compared with 81% for CHWs (P value 0.464). The percentages of unsuccessful outcomes were similar for both groups. CONCLUSIONS: Our study demonstrates the process to engage RHCPs in TB prevention and care. The study highlights community preference for RHCPs as DOT provider who can produce similar TB treatment success rates as that of CHWs identified by programme.

Impact of Advocacy, Communication, Social Mobilization and Active Case Finding on TB Notification in Jharkhand, India.

Community-level benefits of screening for active tuberculosis (TB) disease remain uncertain. Project Axshya (meaning free of TB) conducted advocacy, communication, social mobilization, and active case finding among vulnerable/marginalized populations of India. Among 15 districts of Jharkhand state, the project was initiated in 36 subdistrict level administrative units - tuberculosis units (TUs) in a staggered manner between April 2013 and September 2014, and continued till the end of 2015. Seven TUs did not implement the project. We assessed the relative change in the quarterly TB case finding indicators (n = 4) after inclusion of a TU within the project. By fitting four multilevel models (mixed-effects maximum likelihood regression using random intercept), we adjusted for secular (over previous five quarters) and seasonal trends, baseline differences within Axshya and non-Axshya TUs, and population size and clustering within districts and within TUs. After inclusion of a TU within the project, we found a significant increase [95% confidence interval (CI)] in TU-level presumptive TB sputum examination rate, new sputum-positive TB Case Notification Rate (CNR), sputum-positive TB CNR, and all forms TB CNR by 12 (5.5, 18.5), 1.1 (0.5, 1.7), 1.3 (0.6, 2.0), and 1.2 (0.1, 2.2) per 100,000 population per quarter, respectively. Overall, the project resulted in an increase (95% CI) in sputum examination and detection of new sputum-positive TB, sputum-positive TB and all forms of TB patients by 22,410 (10,203, 34,077), 2066 (923, 3210), 2380 (1162, 3616), and 2122 (203, 4059), respectively. This provides evidence for implementing project Axshya over and above the existing passive case finding.

Diagnostic tools used in the evaluation of acute febrile illness in South India: a scoping review.

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.

Active versus passive case finding for tuberculosis in marginalised and vulnerable populations in India: comparison of treatment outcomes.

Background: Community-based active case finding (ACF) for tuberculosis (TB) implemented among marginalised and vulnerable populations in 285 districts of India resulted in reduction of diagnosis delay and prevalence of catastrophic costs due to TB diagnosis. We were interested to know whether this translated into improved treatment outcomes. Globally, there is limited published literature from marginalised and vulnerable populations on the independent effect of community-based ACF on treatment outcomes when compared to passive case finding (PCF). Objectives: To determine the relative differences in unfavourable treatment outcomes (death, loss-to-follow-up, failure, not evaluated) of ACF and PCF-diagnosed people. Methods: Cohort study involving record reviews and interviews in 18 randomly selected districts. We enrolled all ACF-diagnosed people with new smear-positive pulmonary TB, registered under the national TB programme between March 2016 and February 2017, and an equal number of randomly selected PCF-diagnosed people in the same settings. We used log binomial models to adjust for confounders. Results: Of 572 enrolled, 275 belonged to the ACF and 297 to the PCF group. The proportion of unfavourable outcomes were 10.2% (95% CI: 7.1%, 14.3%) in the ACF and 12.5% (95% CI: 9.2%, 16.7%) in the PCF group (p = 0.468). The association between ACF and unfavourable outcomes remained non-significant after adjusting for confounders available from records [aRR: 0.83 (95% CI: 0.56, 1.21)]. Due to patient non-availability at their residence, interviews were conducted for 465 (81.3%). In the 465 cohort too, there was no association after adjusting for confounders from records and interviews [aRR: 1.05 (95% CI: 0.62, 1.77)]. Conclusion: We did not find significant differences in the treatment outcomes. Due to the wide CIs, studies with larger sample sizes are urgently required. Studies are required to understand how to translate the benefits of ACF to improved treatment outcomes.