Genome-wide identification of MATE and ALMT genes and their expression profiling in mungbean (Vigna radiata L.) under aluminium stress.

The Multidrug and toxic compound extrusion (MATE) and aluminium activated malate transporter (ALMT) gene families are involved in response to aluminium (Al) stress. In this study, we identified 48 MATE and 14 ALMT gene families in Vigna radiata genome and classified into 5 (MATE) and 3 (ALMT) clades by phylogenetic analysis. All the VrMATE and VrALMT genes were distributed across mungbean chromosomes. Tandem duplication was the main driving force for evolution and expansion of MATE gene family. Collinearity of mungbean with soybean indicated that MATE gene family is closely linked to Glycine max. Eight MATE transporters in clade 2 were found to be associated with previously characterized Al tolerance related MATEs in various plant species. Citrate exuding motif (CEM) was present in seven VrMATEs of clade 2. Promoter analysis revealed abundant plant hormone and stress responsive cis-elements. Results from quantitative real time-polymerase chain reaction (qRT-PCR) revealed that VrMATE19, VrMATE30 and VrALMT13 genes were markedly up-regulated at different time points under Al stress. Overall, this study offers a new direction for further molecular characterization of the MATE and ALMT genes in mungbean for Al tolerance.

Development of unique soil organic carbon stability index under influence of integrated nutrient management in four major soil orders of India.

Stability of soil organic carbon (SOC) is pre-requisite for stabilization of C leading to long-term C sequestration. However, development of a comprehensive metric of SOC stability is a major challenge. The objectives for the study were to develop novel SOC stability indices by encompassing physical, chemical, and biochemical SOC stability parameters and identifying the most important indicators from a Mollisol, an Inceptisol, a Vertisol, and an Alfisol under long-term manuring and fertilization. The treatments were control, 100%NPK, 50% NPK+ 50% N through either farmyard manure, cereal residue, or green manure. SOC stability indicators were selected, transformed and integrated into unique SOC stability indices via conceptual framework and principal component analysis. Principal component analysis identified Al-macroaggregate, humic acid C-microaggregate, microaggregate-C, particulate organic matter-C-macroaggregate and polyphenol-microaggregate as the important SOC stability indicators. The principal component analysis -based SOC stability index varied from 0.2 to 0.9, 0.1 to 0.5, 0.2 to 0.6, 0.1 to 0.5 for Mollisol, Inceptisol, Vertisol and Alfisol, respectively. The SOC-stability index derived from conceptual framework and principal component analysis significantly lined up well with one another, although NaOCl-Res-C showed a high correlation with both conceptual framework (r = 0.8) and principal component analysis-based (r = 0.7) SOC stability indexes, suggesting that both methods might be used to quickly assess SOC stability in four soil orders. Overall, 50%NPK+50%N by farmyard manure or green manure emerged as the most effective management practices for enhancing stability of SOC in Mollisol, Inceptisol, Vertisol, and Alfisol of India which might act as major C sink in rice-wheat and maize-wheat cropping systems. The other aspect of C sequestration is to enhance agricultural productivity without depending much on expensive chemical fertilizers. The model yardstick thus developed for assessing SOC stability might be useful to other systems as well.

Linking genome wide RNA sequencing with physio-biochemical and cytological responses to catalogue key genes and metabolic pathways for alkalinity stress tolerance in lentil (Lens culinaris Medikus).

BACKGROUND: Alkaline soils cause low productivity in crop plants including lentil. Alkalinity adaptation strategies in lentil were revealed when morpho-anatomical and physio-biochemical observations were correlated with transcriptomics analysis in tolerant (PDL-1) and sensitive (L-4076) cultivars at seedling stage. RESULTS: PDL-1 had lesser salt injury and performed better as compared to L-4076. Latter showed severe wilting symptoms and higher accumulation of Na+ and lower K+ in roots and shoots. PDL-1 performed better under high alkalinity stress which can be attributed to its higher mitotic index, more accumulation of K+ in roots and shoots and less aberrantly dividing cells. Also, antioxidant enzyme activities, osmolytes' accumulation, relative water content, membrane stability index and abscisic acid were higher in this cultivar. Differentially expressed genes (DEGs) related to these parameters were upregulated in tolerant genotypes compared to the sensitive one. Significantly up-regulated DEGs were found to be involved in abscisic acid (ABA) signalling and secondary metabolites synthesis. ABA responsive genes viz. dehydrin 1, 9-cis-epoxycarotenoid dioxygenase, ABA-responsive protein 18 and BEL1-like homeodomain protein 1 had log2fold change above 4.0. A total of 12,836 simple sequence repeats and 4,438 single nucleotide polymorphisms were identified which can be utilized in molecular studies. CONCLUSIONS: Phyto-hormones biosynthesis-predominantly through ABA signalling, and secondary metabolism are the most potent pathways for alkalinity stress tolerance in lentil. Cultivar PDL-1 exhibited high tolerance towards alkalinity stress and can be used in breeding programmes for improving lentil production under alkalinity stress conditions.

Fab Advances in Fabaceae for Abiotic Stress Resilience: From 'Omics' to Artificial Intelligence.

Legumes are a better source of proteins and are richer in diverse micronutrients over the nutritional profile of widely consumed cereals. However, when exposed to a diverse range of abiotic stresses, their overall productivity and quality are hugely impacted. Our limited understanding of genetic determinants and novel variants associated with the abiotic stress response in food legume crops restricts its amelioration. Therefore, it is imperative to understand different molecular approaches in food legume crops that can be utilized in crop improvement programs to minimize the economic loss. 'Omics'-based molecular breeding provides better opportunities over conventional breeding for diversifying the natural germplasm together with improving yield and quality parameters. Due to molecular advancements, the technique is now equipped with novel 'omics' approaches such as ionomics, epigenomics, fluxomics, RNomics, glycomics, glycoproteomics, phosphoproteomics, lipidomics, regulomics, and secretomics. Pan-omics-which utilizes the molecular bases of the stress response to identify genes (genomics), mRNAs (transcriptomics), proteins (proteomics), and biomolecules (metabolomics) associated with stress regulation-has been widely used for abiotic stress amelioration in food legume crops. Integration of pan-omics with novel omics approaches will fast-track legume breeding programs. Moreover, artificial intelligence (AI)-based algorithms can be utilized for simulating crop yield under changing environments, which can help in predicting the genetic gain beforehand. Application of machine learning (ML) in quantitative trait loci (QTL) mining will further help in determining the genetic determinants of abiotic stress tolerance in pulses.

Using Patient Pathway Analysis to Design Patient-centered Referral Networks for Diagnosis and Treatment of Tuberculosis: The Case of the Philippines.

Background: Tuberculosis (TB) is the 8th leading cause of death in the Philippines. A recent prevalence survey found that there were nearly 70% more cases of tuberculosis than previously estimated. Given these new data, the National TB Program (NTP), operating through a decentralized health system, identified about 58% of the estimated new drug-sensitive (DS) TB patients in 2016. However, the NTP only identified and commenced treatment for around 17% of estimated new drug-resistant patients. In order to reach the remaining 42% of drug-sensitive patients and 83% of drug-resistant patients, it is necessary to develop a better understanding of where patients seek care. Methods: National and regional patient pathway analyses (PPAs) were undertaken using existing national survey and NTP data. The PPA assessed the alignment between patient care seeking and the availability of TB diagnostic and treatment services. Results: Systemic referral networks from the community-level Barangay Health Stations (BHSs) to diagnostic facilities have enabled more efficient detection of drug-sensitive tuberculosis in the public sector. Approximately 36% of patients initiated care in the private sector, where there is limited coverage of appropriate diagnostic technologies. Important differences in the alignment between care seeking patterns and diagnostic and treatment availability were found between regions. Conclusions: The PPA identified opportunities for strengthening access to care for all forms of tuberculosis and for accelerating the time to diagnosis by aligning services to where patients initiate care. Geographic variations in care seeking may guide prioritization of some regions for intensified engagement with the private sector.

Examining the quality of childhood tuberculosis diagnosis in Cambodia: a cross-sectional study.

BACKGROUND: Cambodia is one of the 22 countries with the highest TB burden. While childhood TB is estimated to make up 10-20% of total TB cases in high-burden settings, this proportion ranges from 1.3 to 39.4% throughout Cambodia's provinces, suggesting potential under- and over-diagnosis of childhood TB, subnationally. The proportion of case notifications classified as extrapulmonary TB out of total TB case notifications in children is 87%, greatly exceeding the expected global range of 20-30%. There is a gap in the literature on how childhood TB is diagnosed in resource-poor settings, and the quality of diagnoses. The study's aim is to quantitatively assess the quality of clinician performance and availability of diagnostic tools, for diagnosing childhood TB in high-burden Operational Districts in Cambodia. METHODS: Between August and September of 2015, a cross-sectional study was conducted at referral hospitals and villages in 24 high-burden Operational Districts. 40 clinicians, and 104 parents whose child was recently diagnosed with TB were interviewed. Questionnaires assessed availability of diagnostic tools, and clinician knowledge and practice during a clinical examination. Descriptive statistics were calculated to provide cross-sectional data. RESULTS: Availability of advanced diagnostic tools was low. Only 27.5% of clinicians had Xpert machines available at their facility, and 5% had equipment to perform gastric aspiration. 77.5% of clinicians reported that they had a chest X-ray at their facility, but only 34.6% of parents reported that the clinician conducted a chest X-ray. 72.5% of clinicians could name 5 out of 7 main TB screening criteria; however, parent data suggests that clinicians may not be applying knowledge to practice. The mean number of examinations/tests the clinician conducted during the clinical assessment of the child was 1.64. Of the parents whose child had an enlarged lymph node, 60.22% described lymph node characteristics that were not suggestive of TB. CONCLUSION: Limited availability of diagnostic tools and suboptimal clinician performance highlight where resources should be allocated to improve quality of diagnoses. Further research needs to be done in low burden Operational Districts to determine the capacity of clinicians and health facilities for diagnosing childhood TB, where cases are likely being missed.

A systematic review: effectiveness of mass media campaigns for reducing alcohol-impaired driving and alcohol-related crashes.

BACKGROUND: Mass media campaigns have long been used as a tool for promoting public health. In the past decade, the growth of social media has allowed more diverse options for mass media campaigns. This systematic review was conducted to assess newer evidence from quantitative studies on the effectiveness of mass media campaigns for reducing alcohol-impaired driving (AID) and alcohol-related crashes, particularly after the paper that Elder et al. published in 2004. METHODS: This review focused on English language studies that evaluated the effect of mass media campaigns for reducing AID and alcohol-related crashes, with or without enforcement efforts. A systematic search was conducted for studies published between January 1, 2002 and December 31, 2013. Studies from the review by Elder et al. were added as well. RESULTS: A total of 19 studies met the inclusion criteria for the systematic review, including three studies from the review by Elder et al. Nine of them had concomitant enforcement measures and did not evaluate the impact of media campaigns independently. Studies that evaluated the impact of mass media independently showed reduction more consistently (median -15.1%, range -28.8 to 0%), whereas results of studies that had concomitant enforcement activities were more variable (median -8.6%, range -36.4 to +14.6%). Summary effects calculated from seven studies showed no evidence of media campaigns reducing the risk of alcohol-related injuries or fatalities (RR 1.00, 95% CI = 0.94 to 1.06). CONCLUSIONS: Despite additional decade of evidence, reviewed studies were heterogeneous in their approaches; therefore, we could not conclude that media campaigns reduced the risk of alcohol-related injuries or crashes. More studies are needed, including studies evaluating newly emerging media and cost-effectiveness of media campaigns.

Influence of Environmental Tobacco Smoke on Gingival Pigmentation in Schoolchildren.

PURPOSE: To examine the relationship between environmental tobacco smoke (ETS) and oral pigmentation in schoolchildren. MATERIALS AND METHODS: Oral photographs of 117 systemically healthy, nonsmoking children and young adults (aged 10 to 21 years) were randomly selected from two rural schools. Closed-ended questionnaires were designed for this age group and used to record answers given by the subjects. The subjects were divided into two groups based on age: group 1 (10 to 14 years) and group 2 (15 to 21 years). There were 58 subjects in group 1 and 59 in group 2. Gingival pigmentation was classified using the Melanin Index Score (MIS) into MIS-0 (no pigmentation), MIS-1 (solitary unit(s) of pigmentation in papillary gingiva) and MIS-2 (continuous band extending from 2 neighbouring solitary units). RESULTS: In group 1, 17.24% of subjects displayed MIS-0 compared to only 5.08% in group 2. The difference between the groups was found to be statistically significant according to Student's t-test (p < 0.001). In group 2, 38.98% of subjects showed MIS-2 as compared to only 17.24% subjects in group 1. CONCLUSION: Despite the relatively small sample size, the results of the present study confirmed previously reported findings that ETS has an influence on both the prevalence and the severity of gingival pigmentation.

Results from early programmatic implementation of Xpert MTB/RIF testing in nine countries.

BACKGROUND: The Xpert MTB/RIF assay has garnered significant interest as a sensitive and rapid diagnostic tool to improve detection of sensitive and drug resistant tuberculosis. However, most existing literature has described the performance of MTB/RIF testing only in study conditions; little information is available on its use in routine case finding. TB REACH is a multi-country initiative focusing on innovative ways to improve case notification. METHODS: We selected a convenience sample of nine TB REACH projects for inclusion to cover a range of implementers, regions and approaches. Standard quarterly reports and machine data from the first 12 months of MTB/RIF implementation in each project were utilized to analyze patient yields, rifampicin resistance, and failed tests. Data was collected from September 2011 to March 2013. A questionnaire was implemented and semi-structured interviews with project staff were conducted to gather information on user experiences and challenges. RESULTS: All projects used MTB/RIF testing for people with suspected TB, as opposed to testing for drug resistance among already diagnosed patients. The projects placed 65 machines (196 modules) in a variety of facilities and employed numerous case-finding strategies and testing algorithms. The projects consumed 47,973 MTB/RIF tests. Of valid tests, 7,195 (16.8%) were positive for MTB. A total of 982 rifampicin resistant results were found (13.6% of positive tests). Of all tests conducted, 10.6% failed. The need for continuous power supply was noted by all projects and most used locally procured solutions. There was considerable heterogeneity in how results were reported and recorded, reflecting the lack of standardized guidance in some countries. CONCLUSIONS: The findings of this study begin to fill the gaps among guidelines, research findings, and real-world implementation of MTB/RIF testing. Testing with Xpert MTB/RIF detected a large number of people with TB that routine services failed to detect. The study demonstrates the versatility and impact of the technology, but also outlines various surmountable barriers to implementation. The study is not representative of all early implementer experiences with MTB/RIF testing but rather provides an overview of the shared issues as well as the many different approaches to programmatic MTB/RIF implementation.

Changing epidemic of tuberculosis amidst the COVID-19 pandemic in the Western Pacific Region: analysis of tuberculosis case notifications and treatment outcomes from 2015 to 2022.

Background: Coronavirus disease-2019 (COVID-19) pandemic has deeply impacted tuberculosis (TB) services globally. This study aims to assess the COVID-19 pandemic's impact on TB diagnosis and care and explore associated factors in the Western Pacific Region. Methods: We analysed TB case notifications and treatment outcomes for the Region and 14 selected countries and areas from 2015 to 2022. We further explored differences in reported cases from predicted cases by the UHC service coverage index and Human Development Index (HDI), and the relationship between the Stringency Index and TB case notifications during the pandemic. Findings: TB case notifications declined in 2020 (21%) and 2021 (23%) compared to predicted cases and partly recovered in 2022 (18%). The shortfalls in 2020 and 2021 were more prominent in priority countries with high TB burden, where the decrease in clinically diagnosed pulmonary cases and paediatric cases was particularly pronounced. In priority countries, TB case notifications have a positive relationship with UHC service coverage index and HDI in 2021 and an inverse relationship with Stringency Index during the pandemic. In contrast, treatment outcomes have not changed significantly due to the pandemic across countries in the Region. Interpretation: The COVID-19 pandemic has adversely impacted TB diagnosis and care in the Western Pacific Region, especially TB case detection. Stringent government policies against the pandemic, coupled with weak health systems and suboptimal socio-economic development, may have brought a more profound and prolonged impact in priority countries. Funding: The Korea Disease Control and Prevention Agency and the Japan Ministry of Health, Labour and Welfare.

Effect of fertility levels and stress mitigating chemicals on nutrient content, uptake, intercropping advantage and competition effect in cowpea-baby corn intercropping.

The primary goal of this study was to analyze how various row ratios of intercrops, in conjunction with different fertilizer levels with spray of two stress mitigating chemical, affect nutrient content, land productivity, and economic viability during Summer season. Furthermore, we aimed to explore the competitive dynamics within legume/cereal intercropping systems. Hence, A field experiment at Agriculture University, Kota, during the summers of 2019 and 2020, investigated different cowpea + baby corn intercropping system's intercropping indices, nutrient dynamics, uptake, and post-harvest soil nutrient balance under varying recommended fertilizer levels and foliar spray of stress mitigating chemicals. Using a split-split plot design replicated four times, the experiment involved thirty treatment combinations, including five intercropping techniques viz. Sole cowpea, sole baby corn, cowpea + baby corn 2:1, cowpea + baby corn 3:1, cowpea + baby corn 4:1 in the main plot, three fertility levels viz. 100 %, 125 % and 150 % recommended dose of fertilizer (RDF) in subplots, and two stress mitigation chemicals; CaCl2 0.5 % and KNO3 1% in sub-subplots. The findings revealed notable trends, including nitrogen (N) and (P) content in cowpea seeds and straw, baby corn cobs and fodder, as well as enhanced land-equivalent ratio (LER) and monetary advantage index (MAI) within the cowpea + baby corn 2:1 row ratio. However, despite these advantages, total N and P uptake were markedly higher in sole crops. Notably, sole cowpea demonstrated the highest actual N and P balance and lowest was under sole baby corn. Among the fertility levels, the 150 % RDF level exhibited the most favorable outcomes across various parameters, including LER, MAI, NP content, and uptake in both crops. Additionally, higher fertility levels correlated with increased apparent and actual soil nutrient balances. While, among stress mitigation chemicals, CaCl2 0.5 % resulted in significantly heightened N and P uptake. Hence, to optimize intercropping dynamics and maintain soil nutrient balance, it is advisable to intensify cowpea cultivation along with baby corn in a 2:1 row ratio, utilizing 150 % RDF is beneficial. Additionally, alleviating higher temperature stress during the summer season can be achieved by applying a 0.5 % solution CaCl2 through spraying at the flowering and pod development stages of cowpea.

Alleviating summer heat stress in cowpea-baby corn intercropping with stress-reducing chemicals and fertility variations.

Over the past century, the average surface temperature and recurrent heatwaves have been steadily rising, especially during the summer season, which is affecting the yield potential of most food crops. Hence, diversification in cropping systems with suitable fertilizer management is an urgent need to ensure high yield potential during the summer season. Since intercropping has emerged as an important strategy to increase food production, the present study comprises five intercropping systems in the main plot (sole cowpea, sole baby corn, cowpea + baby corn in 2:1, 3:1, and 4:1 row ratio), three levels of fertilizer viz. 100 (N20 P40), 125 (N25 P50), and 150% (N30 P60) recommended dose of fertilizer (RDF) in the subplot, along with two stress-mitigating chemicals (0.5% CaCl2 and 1% KNO3) in the sub-sub plots. A split-split plot system with four replications was established to carry out the field experiment. The effect of intercropping, fertilizer levels, and stress-mitigating chemicals on crop growth rate (CGR), relative growth rate (RGR), plant temperature, relative water content (RWC) and chlorophyll content of cowpea and baby corn, as well as cowpea equivalent yield (CEY), was investigated during the summer seasons of 2019 and 2020. The experiment was conducted at Agriculture University, Kota (Rajasthan), India. Results showed that CGR, RGR, RWC and chlorophyll content of both crops and CEY were maximum under intercropping of cowpea and baby corn in a 2:1 row ratio compared to other intercropping systems. However, the plant temperature of both crops was significantly lower under this system. CEY, CGR, RGR, and chlorophyll content were considerably greater in the subplots with a fertilizer application of 150% RDF compared to lower levels of fertilizer (100 and 125% RDF). Our findings further show that foliar application of CaCl2 0.5% at the flowering and pod-developing stages of cowpea dramatically boosted CEY, CGR, RGR, RWC, and chlorophyll content of both crops and lowered the plant temperature.

Correction: Expansion of social protection is necessary towards zero catastrophic costs due to TB: The first national TB patient cost survey in the Philippines.

[This corrects the article DOI: 10.1371/journal.pone.0264689.].

Process optimization for manufacture of pearl millet-based dairy dessert by using response surface methodology (RSM).

Kheer, a cereal based dessert containing rice, milk and sugar as major ingredients, is very popular in India and South East Asian countries. A process for manufacturing a dairy dessert based on pearl millet and milk as main ingredients was optimized. During the investigation, the effect of different levels of dairy whitener and pearl millet, and temperature was studied by employing a 3 factor central composite rotatable design version 7.1.6. The best formulation with 18.49% dairy whitener and 6.0% pearl millet and a process temperature of 87.5 °C yielded 46.76% of the product on the basis of the dairy whitener used. This formulation was found to be most appropriate for manufacture of pearl millet-based kheer with predicted scores of 7.62, 7.05, 7.32, 6.97, 6.95 and 7.29 for grain to liquid ratio, consistency, sweetness, grain texture, flavour and overall acceptability respectively.

Clinician perspectives of drug-resistant tuberculosis care services in the Philippines.

BACKGROUND/OBJECTIVES: In the Philippines, treatment success rates for drug-resistant tuberculosis (DR-TB) remains low and little is known about the quality of DR-TB services. This study aimed to explore clinician's perspectives of DR-TB care services. METHODS: We conducted semi-structured in-depth interviews from January-March 2018 with 11 providers selected purposively to explore the barriers associated with DR-TB care service delivery, best practices, and recommendations for enhancing patient care. Emerging themes were organized according to the socio-ecological framework. RESULTS: Five major themes were identified: (1) nurses do not feel empowered; (2) particular patients are left behind and more vulnerable than others; (3) infection control practices, fear, and limited capacity in rural health centers; (4) financial insecurity due to program reimbursement mechanisms; and (5) local government support is limited and requires more involvement in support of DR-TB elimination activities. Best practices focused on tailored approaches that eliminated structural, economic, and motivational barriers for patients. Participants recommended financial support from local government units, nutritional assistance for patients, and refresher training for healthcare workers. CONCLUSION: The findings provide additional understanding regarding the barriers that limit successful DR-TB care delivery and provide critical information to improve clinical practice and develop public health interventions for frontline staff including nurses in the Philippines. These strategies could ultimately reduce disparities associated with access to care and treatment adherence, if implemented.

Epidemiology of dengue reported in the World Health Organization's Western Pacific Region, 2013-2019.

The global burden of dengue, an emerging and re-emerging mosquito-borne disease, increased during the 20-year period ending in 2019, with approximately 70% of cases estimated to have been in Asia. This report describes the epidemiology of dengue in the World Health Organization's Western Pacific Region during 2013-2019 using regional surveillance data reported from indicator-based surveillance systems from countries and areas in the Region, supplemented by publicly available dengue outbreak situation reports. The total reported annual number of dengue cases in the Region increased from 430 023 in 2013 to 1 050 285 in 2019, surpassing 1 million cases for the first time in 2019. The reported case-fatality ratio ranged from 0.19% (724/376 972 in 2014 and 2030/1 050 285 in 2019) to 0.30% (1380/458 843 in 2016). The introduction or reintroduction of serotypes to specific areas caused several outbreaks and rare occurrences of local transmission in places where dengue was not previously reported. This report reinforces the increased importance of dengue surveillance systems in monitoring dengue across the Region.

Early detection of tuberculosis through community-based active case finding in Cambodia.

BACKGROUND: Since 2005, Cambodia's national tuberculosis programme has been conducting active case finding (ACF) with mobile radiography units, targeting household contacts of TB patients in poor and vulnerable communities in addition to routine passive case finding (PCF). This paper examines the differences in the demographic characteristics, smear grades, and treatment outcomes of pulmonary TB cases detected through both active and passive case finding to determine if ACF could contribute to early case finding, considering associated project costs for ACF. METHODS: Demographic characteristics, smear grades, and treatment outcomes were compared between actively (n = 405) and passively (n = 602) detected patients by reviewing the existing programme records (including TB registers) of 2009 and 2010. Additional analyses were performed for PCF cases detected after the ACF sessions (n = 91). RESULTS: The overall cost per case detected through ACF was US$ 108. The ACF approach detected patients from older populations (median age of 55 years) compared to PCF (median age of 48 years; p < 0.001). The percentage of smear-negative TB cases detected through ACF was significantly higher (71.4%) than that of PCF (40.5%). Among smear-positive patients, lower smear grades were observed in the ACF group compared to the PCF group (p = 0.002). A fairly low initial defaulter rate (21 patients, 5.2%) was observed in the ACF group. Once treatment was initiated, high treatment success rates were achieved with 96.4% in ACF and with 95.2% in PCF. After the ACF session, the smear grade of TB patients detected through routine PCF continued to be low, suggesting increased awareness and early case detection. CONCLUSIONS: The community-based ACF in Cambodia was found to be a cost-effective activity that is likely to have additional benefits such as contribution to early case finding and detection of patients from a vulnerable age group, possibly with an extended benefit for reducing secondary cases in the community. Further investigations are required to clarify the primary benefits of ACF in early and increased case detection and to assess its secondary impact on reducing on-going transmission.

The multi-step process of building TB/HIV collaboration in Cambodia.

Tuberculosis and HIV/AIDS have synergistic health impacts in terms of disease development and progression. Therefore, collaborative TB and HIV/AIDS activities are a logical health systems response. However, the establishment of these activities presents a challenge for countries that have strong vertical disease programs that differ in their implementation philosophies. Here, we review the process by which TB/HIV collaboration was established in Cambodia. A cycle of overlapping and mutually reinforcing initiatives - local research; piloted implementation with multiple options; and several rounds of policy formulation guided by a cross-functional Technical Working Group - was used to drive nationwide introduction of a full set of TB/HIV collaborative activities. Senior Ministry of Health officials and partner organizations brought early attention to TB/HIV. Both national programs implemented initial screening and testing interventions, even in the absence of a detailed, overarching framework. The use of multiple options for HIV testing identified which programmatic options worked best, and early implementation and pilots determined what unanswered questions required further research. Local conduct of this research - on co-treatment timing and TB symptom screening - speeded adoption of the results into policy guidance, and clarified the relative roles of the two programs. Roll-out is continuing, and results for a variety of key indicators, including screening PLHIV for TB, and testing TB patients for HIV, are at 70-80% and climbing. This experience in Cambodia illustrates the influence of health research on policy, and demonstrates that clear policy guidance, the pursuit of incremental advances, and the use of different approaches to generate evidence can overcome structural barriers to change and bring direct benefits to patients.

Patient- and Health-System-Related Barriers to Treatment Adherence for Patients with Drug-Resistant Tuberculosis in the Philippines: A Mixed-Methods Study.

Purpose: In the Philippines, drug-resistant tuberculosis (DRTB) is a growing concern. Healthcare workers face challenges in retaining patients with DRTB in care. This study intends to understand their perspectives on the factors that influence patient treatment outcomes and to propose potential programmatic solutions for strengthening care services for the patients. Methods: A mixed-methods study was conducted in the Philippines between December 2017 and March 2018 to understand the major barriers for healthcare workers to provide quality care to DRTB patients across the care continuum. In the quantitative phase, healthcare workers participated in an online survey; in the qualitative phase, in-depth interviews were conducted with a select number of the survey respondents to better understand their survey responses. Results: 272 healthcare workers participated in the survey, and of those, 11 were interviewed. Survey results identified economic constraints, patient perceptions of care, family-related concerns, and limited accessibility to healthcare services as the major patient-related barriers across the care continuum. Major health-system-related barriers were insufficient human resources, lack of financial and political support, and limited knowledge about DRTB by healthcare providers. Interviews revealed more elaborate, contextualized, and nuanced aspects of each of the major challenges. The elaborated patient-related barriers included expenses needed during treatment (e.g., transportation); fear of being stigmatized by family, community, or healthcare staff; worries about adverse drug reactions from medication; a lack of family support; and the location of patients' homes. The health-system-related barriers revealed through interviews included the limited capacities of facility staff to provide DRTB care due to insufficient human resources; the shortage of funds to support treatment completion (e.g., transportation allowance and food package for patients, service vehicles and mobile phone costs for outreach actions at the facility level); and discrimination by healthcare staff against patients with DRTB attributed to the staff's limited knowledge and experiences of treating the patients. Conclusion: This study identified the main barriers for DRTB facility staff in the Philippines from the perspectives of providers. Further exploration of the barriers and best practices in facilities may be useful for improving DRTB care in the Philippines.

Expansion of social protection is necessary towards zero catastrophic costs due to TB: The first national TB patient cost survey in the Philippines.

BACKGROUND: Tuberculosis (TB) is a disease associated with poverty. Moreover, a significant proportion of TB patients face a substantial financial burden before and during TB care. One of the top targets in the End TB strategy was to achieve zero catastrophic costs due to TB by 2020. To assess patient costs related to TB care and the proportion of TB-affected households that faced catastrophic costs, the Philippines National TB Programme (NTP) conducted a national TB patient cost survey in 2016-2017. METHODS: A cross-sectional survey of 1,912 TB patients taking treatment in health facilities engaged with the NTP. The sample consists of 786 drug-sensitive TB (DS-TB) patients in urban facilities, 806 DS-TB patients in rural facilities, and 320 drug-resistant TB (DR-TB) patients. Catastrophic cost due to TB is defined as total costs, consisting of direct medical and non-medical costs and indirect costs net of social assistance, exceeding 20% of annual household income. RESULTS: The overall mean total cost including pre- and post-diagnostic costs was US$601. The mean total cost was five times higher among DR-TB patients than DS-TB patients. Direct non-medical costs and income loss accounted for 42.7% and 40.4% of the total cost of TB, respectively. More than 40% of households had to rely on dissaving, taking loans, or selling their assets to cope with the costs. Overall, 42.4% (95% confidence interval (95% CI): 40.2-44.6) of TB-affected households faced catastrophic costs due to TB, and it was significantly higher among DR-TB patients (89.7%, 95%CI: 86.3-93.0). A TB enabler package, which 70% of DR-TB patients received, reduced catastrophic costs by 13.1 percentage points (89.7% to 76.6%) among DR-TB patients, but only by 0.4 percentage points (42.4% to 42.0%), overall. CONCLUSIONS: TB patients in the Philippines face a substantial financial burden due to TB despite free TB services provided by the National TB Programme. The TB enabler package mitigated catastrophic costs to some extent, but only for DR-TB patients. Enhancing the current social and welfare support through multisectoral collaboration is urgently required to achieve zero catastrophic costs due to TB.