Tuberculosis case notifications and outcomes in Peruvian prisons prior to and during the COVID-19 pandemic: a national-level interrupted time series analysis.

Background: The COVID-19 pandemic has significantly disrupted tuberculosis (TB) programs, making it urgent to focus TB elimination efforts on key populations. People experiencing incarceration are at high risk for TB, however, how COVID-19-related disruptions have impacted incarcerated populations with TB is unknown. Methods: Using Peruvian National TB Program data from Jan 2018 to Dec 2021, an interrupted time series of drug-susceptible (DS) TB case notifications pre- and during COVID-19 was conducted (cut-off date: COVID-19 emergency declaration in Peru, 16 March 2020). The effect of TB care occurring pre-vs. during COVID-19 on TB treatment success in the incarcerated and non-incarcerated populations was explored using logistic regression. Findings: DS-TB cases notified in prisons from Jan 2018 to Dec 2021 (n = 10,134) represented 10% of all cases notified in the country (n = 101,507). In the first week of COVID-19, DS-TB case notifications dropped by 61.2% (95% CI: 59.9-62.7%) in the non-incarcerated population and 17.7% (95% CI: 17.5-17.9%) among the incarcerated population. TB treatment success was significantly lower in people receiving TB care entirely during the COVID-19 pandemic vs. before COVID-19 in the non-incarcerated population (OR: 0.81, 95% CI: 0.78-0.85), but not statistically significantly lower in the incarcerated population (OR: 0.88, 95% CI: 0.76-1.01). Incarceration status was not found to modify the effect of COVID-19 period on TB treatment outcomes (OR: 1.07, 95% CI: 0.92-1.25), although treatment success was higher in the incarcerated population (OR [incarcerated vs. not incarcerated, pre-COVID]: 1.52, 95% CI: 1.39-1.67). Interpretation: Both incarcerated and non-incarcerated populations experienced a large drop in DS-TB case notifications (although higher in the non-incarcerated population). Lower TB treatment success among those receiving care during COVID-19 indicates significant TB service disruptions in the overall population. The finding that incarceration at time of diagnosis was associated with treatment success is plausible in Peru given increased screening and stricter treatment monitoring in prisons. Funding: Canadian Institutes of Health Research (Funding Reference Number: 179418) .

Solicited Cough Sound Analysis for Tuberculosis Triage Testing: The CODA TB DREAM Challenge Dataset.

Cough is a common and commonly ignored symptom of lung disease. Cough is often perceived as difficult to quantify, frequently self-limiting, and non-specific. However, cough has a central role in the clinical detection of many lung diseases including tuberculosis (TB), which remains the leading infectious disease killer worldwide. TB screening currently relies on self-reported cough which fails to meet the World Health Organization (WHO) accuracy targets for a TB triage test. Artificial intelligence (AI) models based on cough sound have been developed for several respiratory conditions, with limited work being done in TB. To support the development of an accurate, point-of-care cough-based triage tool for TB, we have compiled a large multi-country database of cough sounds from individuals being evaluated for TB. The dataset includes more than 700,000 cough sounds from 2,143 individuals with detailed demographic, clinical and microbiologic diagnostic information. We aim to empower researchers in the development of cough sound analysis models to improve TB diagnosis, where innovative approaches are critically needed to end this long-standing pandemic.

Adherence trajectory as an on-treatment risk indicator among drug-resistant TB patients in the Philippines.

INTRODUCTION: High levels of treatment adherence are critical for achieving optimal treatment outcomes among patients with tuberculosis (TB), especially for drug-resistant TB (DR TB). Current tools for identifying high-risk non-adherence are insufficient. Here, we apply trajectory analysis to characterize adherence behavior early in DR TB treatment and assess whether these patterns predict treatment outcomes. METHODS: We conducted a retrospective analysis of Philippines DR TB patients treated between 2013 and 2016. To identify unique patterns of adherence, we performed group-based trajectory modelling on adherence to the first 12 weeks of treatment. We estimated the association of adherence trajectory group with six-month and final treatment outcomes using univariable and multivariable logistic regression. We also estimated and compared the predictive accuracy of adherence trajectory group and a binary adherence threshold for treatment outcomes. RESULTS: Of 596 patients, 302 (50.7%) had multidrug resistant TB, 11 (1.8%) extremely drug-resistant (XDR) TB, and 283 (47.5%) pre-XDR TB. We identified three distinct adherence trajectories during the first 12 weeks of treatment: a high adherence group (n = 483), a moderate adherence group (n = 93) and a low adherence group (n = 20). Similar patterns were identified at 4 and 8 weeks. Being in the 12-week moderate or low adherence group was associated with unfavorable six-month (adjusted OR [aOR] 3.42, 95% CI 1.90-6.12) and final (aOR 2.71, 95% 1.73-4.30) treatment outcomes. Adherence trajectory group performed similarly to a binary threshold classification for the prediction of final treatment outcomes (65.9% vs. 65.4% correctly classified), but was more accurate for prediction of six-month treatment outcomes (79.4% vs. 60.0% correctly classified). CONCLUSIONS: Adherence patterns are strongly predictive of DR TB treatment outcomes. Trajectory-based analyses represent an exciting avenue of research into TB patient adherence behavior seeking to inform interventions which rapidly identify and support patients with high-risk adherence patterns.

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.

Case fatality and recurrent tuberculosis among patients managed in the private sector: A cohort study in Patna, India.

BACKGROUND: A key component of the WHO End TB Strategy is quality of care, for which case fatality is a critical marker. Half of India's nearly 3 million TB patients are treated in the highly unregulated private sector, yet little is known about the outcomes of these patients. Using a retrospective cohort design, we estimated the case fatality ratio (CFR) and rate of recurrent TB among patients managed in the private healthcare sector in Patna, India. METHODS: World Health Partners' Private Provider Interface Agencies (PPIA) pilot project in Patna has treated 89,906 private sector TB patients since 2013. A random sample of 4,000 patients treated from 2014 to 2016 were surveyed in 2018 for case fatality and recurrent TB. CFR is defined as the proportion of patients who die during the period of interest. Treatment CFRs, post-treatment CFRs and rates of recurrent TB were estimated. Predictors for fatality and recurrence were identified using Cox proportional hazards modelling. Survey non-response was adjusted for using inverse probability selection weighting. RESULTS: The survey response rate was 56.0%. The weighted average follow-up times were 8.7 months in the treatment phase and 26.4 months in the post-treatment phase. Unobserved patients were more likely to have less than one month of treatment adherence (32.0% vs. 13.5%) and were more likely to live in rural Patna (21.9% vs. 15.0%). The adjusted treatment phase CFR was 7.27% (5.97%, 8.49%) and at 24 months post-treatment was 3.32% (2.36%, 4.42%). The adjusted 24 month post-treatment phase recurrent TB rate was 3.56% (2.54%, 4.79%). CONCLUSIONS: Our cohort study provides critical estimates of TB patient outcomes in the Indian private sector, and accounts for selection bias. Patients in the private sector in Patna experienced a moderate treatment CFR but rates of recurrent TB and post-treatment fatality were low.

Tuberculosis case fatality in India: a systematic review and meta-analysis.

Introduction: The WHO End TB Strategy calls for a global reduction in the case fatality ratio (CFR) below 5%. India accounts for a third of global tuberculosis (TB) deaths. This systematic review estimated CFRs among Indian patients with TB both during and after treatment. Methods: We systematically searched Medline, Embase and Global Health for eligible studies published between 1 January 2006 and 8 January 2019, including both cohort studies and intervention study control arms that followed Indian patients with TB for fatality either during treatment or post-treatment. From relevant studies we extracted CFRs in addition to study demographics. Study quality was assessed using modified Scottish Intercollegiate Guidelines Network cohort criteria. Sufficiently homogenous studies were pooled using a random effect generalised linear mixed model. A meta-regression was performed to associate study characteristics with resulting CFRs. Results: 218 relevant studies were identified, of which 211 provided treatment phase CFRs. Most patients (92.4%) were treated in the public sector. Quality concerns were identified in 74% of papers. We estimated a pooled treatment phase CFR of 5.16% (95% CI 4.20% to 6.34%) which fell to 3.78% (2.77% to 5.16%) when restricted to 52 high-quality studies. Treatment phase CFRs were higher for paediatric (n=27, 6.50% (2.65% to 10.36%)), drug-resistant (n=43, 14.06% (10.15% to 19.49%)) and HIV-infected (n=35, 10.91% (7.68% to 15.50%)) patients. Nineteen post-treatment CFR studies were too heterogeneous to pool except when restricting to three high-quality studies (2.69% (-0.79% to 6.18%)). Poor study quality (OR=2.27 (2.01 to 2.57)) and tertiary centres patients (OR=1.15 (1.03 to 1.28)) were significantly associated with increased treatment phase case fatality. Conclusions: Case fatality is a critical measure of the quality of TB care. While India's treatment CFRs are in line with WHO targets, several key patient groups remain understudied and most studies suffer from methodological issues. Increased high-quality reporting on patient outcomes will help improve the evidence base on this topic.

Deep learning, computer-aided radiography reading for tuberculosis: a diagnostic accuracy study from a tertiary hospital in India.

In general, chest radiographs (CXR) have high sensitivity and moderate specificity for active pulmonary tuberculosis (PTB) screening when interpreted by human readers. However, they are challenging to scale due to hardware costs and the dearth of professionals available to interpret CXR in low-resource, high PTB burden settings. Recently, several computer-aided detection (CAD) programs have been developed to facilitate automated CXR interpretation. We conducted a retrospective case-control study to assess the diagnostic accuracy of a CAD software (qXR, Qure.ai, Mumbai, India) using microbiologically-confirmed PTB as the reference standard. To assess overall accuracy of qXR, receiver operating characteristic (ROC) analysis was used to determine the area under the curve (AUC), along with 95% confidence intervals (CI). Kappa coefficients, and associated 95% CI, were used to investigate inter-rater reliability of the radiologists for detection of specific chest abnormalities. In total, 317 cases and 612 controls were included in the analysis. The AUC for qXR for the detection of microbiologically-confirmed PTB was 0.81 (95% CI: 0.78, 0.84). Using the threshold that maximized sensitivity and specificity of qXR simultaneously, the software achieved a sensitivity and specificity of 71% (95% CI: 66%, 76%) and 80% (95% CI: 77%, 83%), respectively. The sensitivity and specificity of radiologists for the detection of microbiologically-confirmed PTB was 56% (95% CI: 50%, 62%) and 80% (95% CI: 77%, 83%), respectively. For detection of key PTB-related abnormalities 'pleural effusion' and 'cavity', qXR achieved an AUC of 0.94 (95% CI: 0.92, 0.96) and 0.84 (95% CI: 0.82, 0.87), respectively. For the other abnormalities, the AUC ranged from 0.75 (95% CI: 0.70, 0.80) to 0.94 (95% CI: 0.91, 0.96). The controls had a high prevalence of other lung diseases which can cause radiological manifestations similar to PTB (e.g., 26% had pneumonia, 15% had lung malignancy, etc.). In a tertiary hospital in India, qXR demonstrated moderate sensitivity and specificity for the detection of PTB. There is likely a larger role for CAD software as a triage test for PTB at the primary care level in settings where access to radiologists in limited. Larger prospective studies that can better assess heterogeneity in important subgroups are needed.

Over-the-counter antibiotic dispensing by pharmacies: a standardised patient study in Udupi district, India.

BACKGROUND: Antimicrobial resistance is a global health emergency, and one of the contributing factors is overuse and misuse of antibiotics. India is one of the world's largest consumers of antibiotics, and inappropriate use is potentially widespread. This study aimed to use standardised patients (SPs) to measure over-the-counter antibiotic dispensing in one region. METHODS: Three adults from the local community in Udupi, India, were recruited and trained as SPs. Three conditions, in both adults and children, were considered: diarrhoea, upper respiratory tract infection and acute fever. Adult SPs were used as proxies for the paediatric cases. RESULTS: A total of 1522 SP interactions were successfully completed from 279 pharmacies. The proportion of SP interactions resulting in the provision of an antibiotic was 4.34% (95% CI 3.04% to 6.08%) for adult SPs and 2.89% (95% CI 1.8% to 4.4%) for child SPs. In the model, referral to another provider was associated with an OR 0.38 (95% CI 0.18 to 0.79), the number of questions asked was associated with an OR 1.54 (95% CI 1.30 to 1.84) and an SP-pharmacist interaction lasting longer than 3 min was associated with an OR 3.03 (95% CI 1.11 to 8.27) as compared with an interaction lasting less than 1 min. CONCLUSION: Over-the-counter antibiotic dispensing rate was low in Udupi district and substantially lower than previously published SP studies in other regions of India. Dispensing was lowest when pharmacies referred to a doctor, and higher when pharmacies asked more questions or spent more time with clients.

Cost and operational impact of promoting upfront GeneXpert MTB/RIF test referrals for presumptive pediatric tuberculosis patients in India.

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.

Knowledge about tuberculosis and infection prevention behavior: A nine city longitudinal study from India.

BACKGROUND: Improving patients' tuberculosis (TB) knowledge is a salient component of TB control strategies. Patient knowledge of TB may encourage infection prevention behaviors and improve treatment adherence. The purpose of this study is to examine how TB knowledge and infection prevention behaviors change over the course of treatment. METHODS: A matched patient-health worker dataset (n = 6,031) of publicly treated TB patients with NGO-provided treatment support health workers was compiled in nine Indian cities from March 2013 to September 2014. At the beginning and end of TB treatment, patients were asked about their knowledge of TB symptoms, transmission, and treatment and infection prevention behaviors. RESULTS: Patients beginning TB treatment (n = 3,424) demonstrated moderate knowledge of TB; 52.5% (50.8%, 54.2%) knew that cough was a symptom of TB and 67.2% (65.6%, 68.7%) knew that TB was communicable. Overall patient knowledge was significantly associated with literacy, education, and income, and was higher at the end of treatment than at the beginning (3.7%, CI: 3.02%, 4.47%). Infection prevention behaviors like covering a cough (63.4%, CI: 61.2%, 65.0%) and sleeping separately (19.3%, CI: 18.0%, 20.7%) were less prevalent. The age difference between patient and health worker as well as a shared language significantly predicted patient knowledge and adherence to infection prevention behaviors. CONCLUSIONS: Social proximity between health worker and patients predicted greater knowledge and adherence to infection prevention behaviors but the latter rate remains undesirably low.

Upfront Xpert MTB/RIF testing on various specimen types for presumptive infant TB cases for early and appropriate treatment initiation.

BACKGROUND: Diagnosis of tuberculosis (TB) in infants is challenging due to non-specific clinical presentations of the disease in this age-group and low sensitivity of widely available TB diagnostic tools, which in turn delays prompt access to TB treatment. Upfront access to Xpert/MTB RIF (Xpert) testing, a highly sensitive and specific rapid diagnostic tool, could potentially address some of these challenges. Under the current project, we assessed the utility and feasibility of applying upfront Xpert for diagnosis of tuberculosis in infants, including for testing of non-sputum specimens. METHODS: A high throughput lab was established in each of the four project cities, and linked to various health care providers across the city, through rapid specimen transportation and electronic reporting linkages. Free Xpert testing was offered to all infant (<2 years of age) presumptive TB cases (both pulmonary and extra-pulmonary) seeking care at public and private health facilities. RESULTS: A total of 7,994 presumptive infant TB cases were enrolled in the project from April 2014 to October 2016, detecting 465 (5.8%, CI: 5.3-6.4) TB cases. The majority (93.9%; CI: 93.4-94.4) of patient specimens were non-sputum and TB positivity was higher amongst non-sputum specimens. Further, a high proportion (5.6% CI 3.8-8.1) of infant TB cases were found to be rifampicin resistant. Covering large cities with a single lab per city over more than two years, the project demonstrated the feasibility of same-day diagnosis with upfront Xpert testing. This in turn led to prompt treatment initiation, with a two-day median turnaround time to treatment initiation. Case mortality observed in the project cohort of diagnosed TB cases was 11.0% (CI 8.4-14.1), the majority of which was pre- or early treatment mortality, in spite of prompt access to treatment for most diagnosed cases. CONCLUSION: The current project demonstrated the feasibility of applying rapid and upfront Xpert testing for presumptive infant TB cases. Rapid TB diagnosis in turn facilitates prompt and appropriate treatment initiation. Further, levels of rifampicin resistance observed in infants TB cases highlight the additional benefit of upfront resistance testing. However, high rates of early case mortality, in spite of prompt diagnosis and treatment initiation, highlight the need for further research in infant patient pathways for overall improvement in TB care for infant populations.

Prevalence of diabetes mellitus amongst hospitalized tuberculosis patients at an Indian tertiary care center: A descriptive analysis.

BACKGROUND: India has a high prevalence of tuberculosis (TB) as well as diabetes mellitus (DM). DM is a chronic disease caused by deficiency of insulin production by the pancreas. The risk of TB amongst DM patients is three times higher than those without. The estimated national prevalence of DM is 7.3%. Despite the growing burden of DM, there are limited studies describing the prevalence of TB-DM in India. OBJECTIVE: Our study estimated the prevalence of DM amongst adult hospitalized TB patients at Kasturba Hospital, Manipal and determined factors associated with the likelihood of DM-TB co-prevalence. METHODS: We conducted a retrospective cohort study at Kasturba Hospital, Manipal Academy of Higher Education. All hospitalized adult patients diagnosed with pulmonary TB (PTB) and extrapulmonary TB (EPTB) between June 1st 2015 and June 30th 2016 were eligible for inclusion. Pediatric and pregnant TB patients were excluded from our study. Data were extracted from medical charts. Descriptive and multivariate analyses were performed in R. Multivariate analysis adjusted for age, gender, type of TB, history of TB, and nutrition (body mass index (BMI)) status. RESULTS: A total of 728 patients met the eligibility criteria, 517 (71%) were male, 210 (29%) female, 406 (56%) had PTB and 322 (44%) had EPTB. Amongst those with a nutritional status, 36 (30%) patients were underweight (BMI <18.4 kg/m2), 73 (40%) had a normal BMI (18.5kg/m2-24.9 kg/m2), 15 (8%) were overweight (BMI 25.0 kg/m2-29.9 kg/m2) and 9 (5%) were obese (BMI >30.0 kg/m2). A total of 720 (98.9%) of TB patients had at least one blood sugar test result. The overall prevalence of DM (n = 184) amongst TB patients was 25.3% (95% CI 22.2%, 28.6%). When stratified, it was 35.0% (30.4%, 39.9%) and 13.0% (9.7%, 17.3%) amongst PTB and EPTB patients respectively. TB patients aged 41-60 years had 3.51 times higher odds (aOR 3.51 (2.08, 6.07)) of having DM than patients 40 years or younger. Patients aged 60 years or older had 2.49 times higher odds (aOR 2.49 (1.28, 4.85)) of having DM than younger patients (<40 years). Females had lower odds (aOR 0.80 (0.46, 1.37)) of developing DM than male TB patients and patients with a history of TB had lower odds (aOR 0.73 (0.39, 1.32)) than newly diagnosed TB patients. Additionally, EPTB patients had significantly lower odds (aOR 0.26 (0.15, 0.43)) compared to PTB patients. Underweight patients also had significantly lower odds (aOR 0.25 (0.14, 0.42)) of having DM than normal weight patients. CONCLUSION: Our study found a higher prevalence of TB-DM than the national average. TB-DM co-prevalence was significantly associated with age, type of TB and undernutrition. As India's DM prevalence is expected to rise, TB-DM will become an increasingly important part of the TB epidemic requiring specialized study and care.

A bibliometric analysis of tuberculosis research, 2007-2016.

BACKGROUND: Tuberculosis (TB) research is a key component of the End TB Strategy. To track research output, we conducted a bibliometric analysis of TB research from the past decade. METHODS: The Web of Science database was searched for publications from January 2007 to December 2016 with "tuberculosis" in the title. References were analysed using the R bibliometrix package. A year-stratified 5% random subset was drawn to extract funding sources and identify research areas. FINDINGS: The annual growth rate of publications was 7.3%, and was highest (13.1%) among Brazil, Russia, India, China and South Africa (BRICS). The USA was the most productive country, with 18.4% of references, followed by India (9.7%), China (7.3%), England (6.5%), and South Africa (3.9%). In the subset analysis, the most common research area was 'fundamental research' (33.8%). Frequently acknowledged funders were US and EU-based, with China and India emerging as top funders. Collaborations appeared more frequently between high-income countries and low/medium income countries (LMICs), with fewer collaborations among LMICs. CONCLUSION: The past decade has seen a continued increase in TB publications. While USA continues to dominate research output and funding, BRICS countries have emerged as major research producers and funders. Collaborations among BRICS would enhance future TB research productivity.

Accelerating access to quality TB care for pediatric TB cases through better diagnostic strategy in four major cities of India.

BACKGROUND: Diagnosis of TB in children is challenging, and is largely based on positive history of contact with a TB case, clinical and radiological findings, often without microbiological confirmation. Diagnostic efforts are also undermined by challenges in specimen collection and the limited availability of high sensitivity, rapid diagnostic tests that can be applied with a quick turnaround time. The current project was undertaken in four major cities of India to address TB diagnostic challenges in pediatric population, by offering free of cost Xpert testing to pediatric presumptive TB cases, thereby paving the way for better TB care. METHODS: A high throughput lab was established in each of the four project cities, and linked to various health care providers across the city through rapid specimen transportation and electronic reporting linkages. Free Xpert testing was offered to all pediatric (0-14 years) presumptive TB cases (both pulmonary and extra-pulmonary) seeking care at public and private health facilities. RESULTS: The current project enrolled 42,238 pediatric presumptive TB cases from April, 2014 to June, 2016. A total of 3,340 (7.91%, CI 7.65-8.17) bacteriologically confirmed TB cases were detected, of which 295 (8.83%, CI 7.9-9.86) were rifampicin-resistant. The level of rifampicin resistance in the project cohort was high. Overall Xpert yielded a high proportion of valid results and TB detection rates were more than three-fold higher than smear microscopy. The project provided same-day testing and early availability of results led to rapid treatment initiation and success rates and very low rates of treatment failure and loss to follow-up. CONCLUSION: The current project demonstrated the feasibility of rolling out rapid and upfront Xpert testing for pediatric presumptive TB cases through a single Xpert lab per city in an efficient manner. Rapid turnaround testing time facilitated prompt and appropriate treatment initiation. These results suggest that the upfront Xpert assay is a promising solution to address TB diagnosis in children. The high levels of rifampicin resistance detected in presumptive pediatric TB patients tested under the project are a major cause of concern from a public health perspective which underscores the need to further prioritize upfront Xpert access to this vulnerable population.

Performance of the Xpert HIV-1 Viral Load Assay: a Systematic Review and Meta-analysis.

Viral load (VL) is the preferred treatment-monitoring approach for HIV-positive patients. However, more rapid, near-patient, and low-complexity assays are needed to scale up VL testing. The Xpert HIV-1 VL assay (Cepheid, Sunnyvale, CA) is a new, automated molecular test, and it can leverage the GeneXpert systems that are being used widely for tuberculosis diagnosis. We systematically reviewed the evidence on the performance of this new tool in comparison to established reference standards. A total of 12 articles (13 studies) in which HIV patient VLs were compared between Xpert HIV VL assay and a reference standard VL assay were identified. Study quality was generally high, but substantial variability was observed in the number and type of agreement measures reported. Correlation coefficients between Xpert and reference assays were high, with a pooled Pearson correlation (n = 8) of 0.94 (95% confidence interval [CI], 0.89, 0.97) and Spearman correlation (n = 3) of 0.96 (95% CI, 0.86, 0.99). Bland-Altman metrics (n = 11) all were within 0.35 log copies/ml of perfect agreement. Overall, Xpert HIV-1 VL performed well compared to current reference tests. The minimal training and infrastructure requirements for the Xpert HIV-1 VL assay make it attractive for use in resource-constrained settings, where point-of-care VL testing is most needed.