An Effective Health System Approach to End TB: Implementing the Double X Strategy in Vietnam.

Countries that are high burden for TB must reverse the COVID-19 pandemic's devastating effects to accelerate progress toward ending TB. Vietnam's Double X (2X) strategy uses chest radiography (CXR) and GeneXpert (Xpert) rapid diagnostic testing to improve early detection of TB disease. Household contacts and vulnerable populations (e.g., individuals aged 60 years and older, smokers, diabetics, those with alcohol use disorders, and those previously treated for TB) with and without TB symptoms were screened in community campaigns using CXRs, followed by Xpert for those with a positive screen. In public non-TB district facilities, diabetics, respiratory outpatients, inpatients with lung disease, and other vulnerable populations underwent 2X evaluation. During COVID-19 restrictions in Vietnam, the 2X strategy improved access to TB services by decentralization to commune health stations, the lowest level of the health system, and enabling self-screening using a quick response mobile application. The number needed to screen (NNS) with CXRs to diagnose 1 person with TB disease was calculated for all 2X models and showed the highest yield among self-screeners (11 NNS with CXR), high yield for vulnerable populations in communities (60 NNS) and facilities (19 NNS), and moderately high yield for household contacts in community campaigns (154 NNS). Computer-aided diagnosis for CXRs was incorporated into community and facility implementation and improved physicians' CXR interpretations and Xpert referral decisions. Integration of TB infection and TB disease evaluation increased eligibility for TB preventive treatment among household contacts, a major challenge during implementation. The 2X strategy increased the rational use of Xpert, employing a health system-wide approach that reached vulnerable populations with and without TB symptoms in communities and facilities for early detection of TB disease. This strategy was effectively adapted to different levels of the health system during COVID-19 restrictions and contributed to post-pandemic TB recovery in Vietnam.

Computer-Aided Detection for Chest Radiography to Improve the Quality of Tuberculosis Diagnosis in Vietnam's District Health Facilities: An Implementation Study.

In Vietnam, chest radiography (CXR) is used to refer people for GeneXpert (Xpert) testing to diagnose tuberculosis (TB), demonstrating high yield for TB but a wide range of CXR abnormality rates. In a multi-center implementation study, computer-aided detection (CAD) was integrated into facility-based TB case finding to standardize CXR interpretation. CAD integration was guided by a programmatic framework developed for routine implementation. From April through December 2022, 24,945 CXRs from TB-vulnerable populations presenting to district health facilities were evaluated. Physicians interpreted all CXRs in parallel with CAD (qXR 3.0) software, for which the selected TB threshold score was ≥0.60. At three months, there was 47.3% concordance between physician and CAD TB-presumptive CXR results, 7.8% of individuals who received CXRs were referred for Xpert testing, and 858 people diagnosed with Xpert-confirmed TB per 100,000 CXRs. This increased at nine months to 76.1% concordant physician and CAD TB-presumptive CXRs, 9.6% referred for Xpert testing, and 2112 people with Xpert-confirmed TB per 100,000 CXRs. Our programmatic CAD-CXR framework effectively supported physicians in district facilities to improve the quality of referral for diagnostic testing and increase TB detection yield. Concordance between physician and CAD CXR results improved with training and was important to optimize Xpert testing.

Prescription practice of anti-tuberculosis drugs in Yunnan, China: A clinical audit.

OBJECTIVES: China has a high burden of drug-resistant tuberculosis (TB). As irrational use and inadequate dosing of anti-TB drugs may contribute to the epidemic of drug-resistant TB, we assessed the drug types and dosages prescribed in the treatment of TB cases in a representative sample of health care facilities in Yunnan. METHODS: We applied multistage cluster sampling using probability proportion to size to select 28 counties in Yunnan. Consecutive pulmonary TB patients were enrolled from either the TB centers of Yunnan Center of Disease Control or designated TB hospitals. Outcomes of interest included the regimen used in the treatment of new and retreatment TB patients; and the proportion of patients treated with adequate dosing of anti-TB drugs. Furthermore, we assess whether there has been reduction in the use of fluoroquinolone and second line injectables in Tuberculosis Clinical Centre (TCC) after the training activity in late 2012. RESULTS: Of 2390 TB patients enrolled, 582 (24.4%) were prescribed second line anti-TB drugs (18.0% in new cases and 60.9% in retreatment cases); 363(15.2%) prescribed a fluoroquinolone. General hospitals (adjusted odds ratio (adjOR) 1.97, 95% confidence interval (CI) 1.47-2.66), retreatment TB cases (adjOR 4.75, 95% CI 3.59-6.27), smear positive cases (adjOR 1.69, 95% CI 1.22-2.33), and extrapulmonary TB (adjOR 2.59, 95% CI 1.66-4.03) were significantly associated with the use of fluoroquinolones. The proportion of patients treated with fluoroquinolones decreased from 41.4% before 2013 to 13.5% after 2013 (adjOR 0.19, 95% CI 0.12-0.28) in TCC. The proportion of patients with correct, under and over dosages of isoniazid was 88.2%, 1.5%, and 10.4%, respectively; of rifampicin was 50.2%, 46.8%, and 2.9%; of pyrazinamide was 67.6%, 31.7% and 0.7%; and of ethambutol was 41.4%, 57.5%, and 1.0%. CONCLUSIONS: The prescribing practice of anti-TB drugs was not standardized, findings with significant programmatic implication.

Preventing emergence of drug resistant tuberculosis in Myanmar's transitioning health system.

Multidrug-resistant tuberculosis (MDR-TB) is a particular threat to the populations of resource-limited countries. Although inadequate treatment of TB has been identified as a major underlying cause of drug resistance, essential information to inform changes in health service delivery and policy is missing. We investigate factors that may be driving the emergence of MDR-TB in Myanmar, a country where investment and health system reforms are ongoing to address the unexplained, high occurrence of MDR-TB. We conducted a multi-centre, retrospective case-control study in 10 townships across Yangon. Cases were 202 GeneXpert-confirmed MDR-TB patients with a history of prior first-line treatment for TB. Controls were 404 previously untreated smear-microscopy confirmed TB patients who had no evidence of resistance to anti-TB drugs. Information on patient and health service factors was collected through face-to-face patient interviews and hospital record reviews. Multivariable logistic regression analysis indicated that the following TB patient groups are at higher risk of developing MDR-TB after initial TB treatment: those who have diabetes (aOR 2.10; 95% CI 1.17-3.76), those who missed taking drugs during the initial treatment more than once weekly (aOR 2.35; 95% CI 1.18-4.65) and those with a higher socioeconomic (aOR 1.99; 95% CI 1.09-3.63) or educational status (aOR 1.78; 95% CI1.01-3.13). Coinciding with a surge in funding to improve health in Myanmar, this study identifies practices of patients and healthcare organizations that can be addressed, and high-risk TB patient groups that can be prioritized for treatment support. Specifically, the study shows that TB patients who experience frequent, short interruptions in treatment and those with diabetes may require enhanced treatment support and monitoring by health services in order to prevent further generation of drug resistance.

Electronic health, telemedicine, and new paradigms for training and care.

PURPOSE OF REVIEW: HIV prevention and care is changing rapidly; guideline revisions and programmatic scale-up require innovative approaches to in-service training and care extension to improve provider practice and care access. We assessed recent (≤12 months) peer-reviewed publications on electronic health (eHealth), telemedicine, and other innovative provider-targeted interventions for HIV-related care. RECENT FINDINGS: Key developments included systems merging electronic medical records (EMR) with provider clinical decision aids to prompt action, demonstration eHealth, and telemedicine projects, reviews or descriptions of technology to improve connectivity in lower resource settings, and a few trials on provider-centered interventions. Most publications were program reports and few data were available regarding efficacy of eHealth interventions for providers on patient HIV-related outcomes, notably identification and management of antiretroviral treatment failure in Kenya. Better evidence is needed for strategies to train providers and care extenders with the goal to improve impact of HIV prevention and care interventions. SUMMARY: Rapid technology introduction and expansion may change the paradigm for improving provider knowledge and practice. Although new, the developments are promising for HIV provider-targeted eHealth and innovations for traditional training. More rigorous testing with randomized trials is needed to demonstrate impact on services for people living with HIV.

The H antigen at epithelial surfaces is associated with susceptibility to asthma exacerbation.

RATIONALE: Acute asthma exacerbations, precipitated by viral infections, are a significant cause of morbidity, but not all patients with asthma are equally susceptible. OBJECTIVES: To explore susceptibility factors for asthma exacerbations, we considered a role for histoblood group antigens because they are implicated in mechanisms of gastrointestinal viral infection, specifically the O-secretor mucin glycan phenotype. We investigated if this phenotype is associated with susceptibility to asthma exacerbation. METHODS: We performed two consecutive case-control studies in subjects with asthma who were either prone or resistant to asthma exacerbations. Exacerbation-prone cases had frequent use of prednisone for an asthma exacerbation and frequent asthma-related healthcare utilization, whereas exacerbation-resistant control subjects had rarely reported asthma exacerbations. The frequency of different mucin glycan phenotypes, defined by the presence or absence of H (O), A, B, or AB antigens, was compared in cases and control subjects. MEASUREMENTS AND MAIN RESULTS: In an initial study consisting of 49 subjects with asthma (23 cases and 26 control subjects), we found that having the O-secretor phenotype was associated with a 5.8-fold increase in the odds of being a case (95% confidence interval, 1.7-21.0; P = 0.006). In a replication study consisting of 204 subjects with asthma (101 cases and 103 control subjects), we found that having the O-secretor phenotype was associated with a 2.3-fold increased odds of being a case (95% confidence interval, 1.2-4.4; P = 0.02). CONCLUSIONS: The O-secretor mucin glycan phenotype is associated with susceptibility to asthma exacerbation. Clinical trial registered at www.clinicaltrials.gov (NCT00201266).

Roles of epithelial cell-derived periostin in TGF-beta activation, collagen production, and collagen gel elasticity in asthma.

Periostin is considered to be a matricellular protein with expression typically confined to cells of mesenchymal origin. Here, by using in situ hybridization, we show that periostin is specifically up-regulated in bronchial epithelial cells of asthmatic subjects, and in vitro, we show that periostin protein is basally secreted by airway epithelial cells in response to IL-13 to influence epithelial cell function, epithelial-mesenchymal interactions, and extracellular matrix organization. In primary human bronchial epithelial cells stimulated with periostin and epithelial cells overexpressing periostin, we reveal a function for periostin in stimulating the TGF-beta signaling pathway in a mechanism involving matrix metalloproteinases 2 and 9. Furthermore, conditioned medium from the epithelial cells overexpressing periostin caused TGF-beta-dependent secretion of type 1 collagen by airway fibroblasts. In addition, mixing recombinant periostin with type 1 collagen in solution caused a dramatic increase in the elastic modulus of the collagen gel, indicating that periostin alters collagen fibrillogenesis or cross-linking and leads to stiffening of the matrix. Epithelial cell-derived periostin in asthma has roles in TGF-beta activation and collagen gel elasticity in asthma.

Rheologic properties of sinonasal mucus in patients with chronic sinusitis.

BACKGROUND: Mucociliary clearance is impaired in chronic rhinosinusitis (CRS). Clearance of sinonasal secretions is influenced by its rheological properties. The purpose of this study was to describe the rheological properties of sinonasal mucus in patients with CRS and correlate them with disease severity. METHODS: Twenty-three adult subjects with CRS underwent collection of sinonasal secretions. Samples were analyzed using the AR2000 cone and plate rheometer (TA Instruments, New Castle, DE) to determine the dynamic viscosity and elasticity. These properties were used to calculate mucus clearance indices. All patients completed the Sinonasal Outcome Test (SNOT-20). Recent sinus computed tomography (CT) scans were electronically reviewed and scored according to the Lund-McKay staging system. RESULTS: The mean dynamic elasticity and viscosity of sinus mucus at 1 Hz were 78.24 +/- 103.4 Pa and 22.09 +/- 29.62 Pa, respectively. The mean elasticity and viscosity values at 10 Hz were 118.9 +/- 155.5 Pa and 32.36 +/- 45.58 Pa, respectively. Three indices of disease severity (SNOT-20 score, Lund-McKay score, and nasal polyps) correlated with increased mucus viscoelasticity and/or worsened mucociliary clearance indices (MCIs). CONCLUSION: This study establishes the range of rheological properties of sinonasal mucus in patients with CRS and suggests an association between disease severity and MCIs.

Ex vivo sputum analysis reveals impairment of protease-dependent mucus degradation by plasma proteins in acute asthma.

RATIONALE: Airway mucus plugs, composed of mucin glycoproteins mixed with plasma proteins, are an important cause of airway obstruction in acute severe asthma, and they are poorly treated with current therapies. OBJECTIVES: To investigate mechanisms of airway mucus clearance in health and in acute severe asthma. METHODS: We collected airway mucus from patients with asthma and nonasthmatic control subjects, using sputum induction or tracheal aspiration. We used rheological methods complemented by centrifugation-based mucin size profiling and immunoblotting to characterize the physical properties of the mucus gel, the size profiles of mucins, and the degradation products of albumin in airway mucus. MEASUREMENTS AND MAIN RESULTS: Repeated ex vivo measures of size and entanglement of mucin polymers in airway mucus from nonasthmatic control subjects showed that the mucus gel is normally degraded by proteases and that albumin inhibits this degradation. In airway mucus collected from patients with asthma at various time points during acute asthma exacerbation, protease-driven mucus degradation was inhibited at the height of exacerbation but was restored during recovery. In immunoblots of human serum albumin digested by neutrophil elastase and in immunoblots of airway mucus, we found that albumin was a substrate of neutrophil elastase and that products of albumin degradation were abundant in airway mucus during acute asthma exacerbation. CONCLUSIONS: Rheological methods complemented by centrifugation-based mucin size profiling of airway mucins in health and acute asthma reveal that mucin degradation is inhibited in acute asthma, and that an excess of plasma proteins present in acute asthma inhibits the degradation of mucins in a protease-dependent manner. These findings identify a novel mechanism whereby plasma exudation may impair airway mucus clearance.

Epithelial mucin stores are increased in the large airways of smokers with airflow obstruction.

BACKGROUND: Habitual cigarette smoking is associated with chronic mucus hypersecretion, but the relationship between mucus abnormalities and airflow obstruction in smokers is uncertain. METHODS: We collected bronchial biopsy samples and epithelial brushings from 24 smokers with and without airflow obstruction and 19 nonsmoking healthy control subjects. Epithelial mucin stores, mucin immunostains, and goblet cell morphology were quantified in bronchial biopsy samples using stereology, and mucin gene expression was quantified in epithelial brushings using real-time reverse transcriptase-polymerase chain reaction. RESULTS: Goblet cell size and number were higher than normal in smokers (both p < 0.05), leading to a 2.2-fold increase in the volume of stored mucin in the epithelium per surface area of basal lamina (1.94 +/- 0.31 microm(3)/microm(2) vs 4.32 +/- 0.55 microm(3)/microm(2) in control subjects vs smokers, p = 0.001). The increase in stored mucin occurred because of an increase in MUC5AC (p = 0.018) and despite a decrease in MUC5B (p < 0.0001). Stored mucin was significantly higher in the subgroup of smokers with airflow obstruction (p = 0.029) and correlated with FEV(1)/FVC even when controlling for diffusing capacity as a measure of emphysema (p = 0.034). CONCLUSIONS: Epithelial mucin stores are increased in habitual smokers because of goblet cell hypertrophy and hyperplasia, and the pattern of mucin gene expression is abnormal. The highest epithelial mucin stores are found in smokers with airflow obstruction, suggesting a mechanistic link between epithelial mucin dysregulation and airflow obstruction.