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Wondu Teshome,1 Mihretu Belayneh,1 Mathewos Moges,1 Misganu Endriyas,2 Emebet Mekonnen,2 Sinafiksh Ayele,2 Tebeje Misganaw,2 Mekonnen Shiferaw,2 Palanivel Chinnakali,3 Sven Gudmund Hinderaker,4 Ajay MV Kumar5 1School of Public and Environmental Health, College of Medicine and Health Sciences, Hawassa University, Hawassa, Ethiopia; 2Research Technology Transfer Process Unit, SNNP Regional Health Bureau, Hawassa, Ethiopia; 3Department of Preventive and Social Medicine, Jawaharlal Institute of Post-graduate Medical Education and Research, Puducherry, India; 4Centre for International Health, University of Bergen, Bergen, Norway; 5The International Union Against Tuberculosis and Lung Disease, South-East Asia Regional Office, New Delhi, India Background: Treatment adherence is critical for the success of antiretroviral therapy (ART) for people living with HIV. There is limited representative information on ART drug adherence and its associated factors from Southern Ethiopia. We aimed at estimating the level of adherence to ART among people living with HIV and factors associated with it in 20 randomly selected ART clinics of Southern Ethiopia.Methods: In this cross-sectional study, we interviewed consecutive HIV patients on first-line antiretroviral regimen attending the clinics in June 2014 using a pretested and structured questionnaire. For measuring adherence, we used 4-day recall method based on “The AIDS Clinical Trial Group adherence assessment tool”. Patients were classified as “Incomplete adherence” if they missed any of the doses in the last 4 days. Data were singly entered using EpiData and descriptive analysis, and unadjusted odds ratios were calculated using EpiDataStat software. Multivariate logistic regression analysis was performed using Stata v12.0.Results: Of 974 patients interviewed, 539 (56%) were females, and mean age was 35 years. The proportion of patients with incomplete adherence was 13% (95% confidence interval: 11%–15%). In multivariate analysis, factors significantly associated with incomplete adherence included young age, being Protestant Christian, consuming alcohol, being single, and being a member of an HIV association. Psychosocial factors like stigma, depression, and satisfaction to care were not associated with incomplete adherence in the current context.Conclusion: The overall adherence to ART was good. However, there were certain subgroups with incomplete adherence who need special attention. The health care providers (especially counselors) need to be aware of these subgroups and tailor their counseling to improve adherence among these groups. Exploratory qualitative studies may help uncover the exact reasons for incomplete adherence. Keywords: operational research, SORT IT, treatment compliance

Background: India accounts for about one-quarter of people contracting tuberculosis (TB) disease annually and nearly one-third of TB deaths globally. Many Indians do not navigate all care cascade stages to receive TB treatment and achieve recurrence-free survival. Guided by a population/exposure/comparison/outcomes (PECO) framework, we report findings of a systematic review to identify factors contributing to unfavorable outcomes across each care cascade gap for TB disease in India., Methods and Findings: We defined care cascade gaps as comprising people with confirmed or presumptive TB who did not: start the TB diagnostic workup (Gap 1), complete the workup (Gap 2), start treatment (Gap 3), achieve treatment success (Gap 4), or achieve TB recurrence-free survival (Gap 5). Three systematic searches of PubMed, Embase, and Web of Science from January 1, 2000 to August 14, 2023 were conducted. We identified articles evaluating factors associated with unfavorable outcomes for each gap (reported as adjusted odds, relative risk, or hazard ratios) and, among people experiencing unfavorable outcomes, reasons for these outcomes (reported as proportions), with specific quality or risk of bias criteria for each gap. Findings were organized into person-, family-, and society-, or health system-related factors, using a social-ecological framework. Factors associated with unfavorable outcomes across multiple cascade stages included: male sex, older age, poverty-related factors, lower symptom severity or duration, undernutrition, alcohol use, smoking, and distrust of (or dissatisfaction with) health services. People previously treated for TB were more likely to seek care and engage in the diagnostic workup (Gaps 1 and 2) but more likely to suffer pretreatment loss to follow-up (Gap 3) and unfavorable treatment outcomes (Gap 4), especially those who were lost to follow-up during their prior treatment. For individual care cascade gaps, multiple studies highlighted lack of TB knowledge and structural barriers (e.g., transportation challenges) as contributing to lack of care-seeking for TB symptoms (Gap 1, 14 studies); lack of access to diagnostics (e.g., X-ray), non-identification of eligible people for testing, and failure of providers to communicate concern for TB as contributing to non-completion of the diagnostic workup (Gap 2, 17 studies); stigma, poor recording of patient contact information by providers, and early death from diagnostic delays as contributing to pretreatment loss to follow-up (Gap 3, 15 studies); and lack of TB knowledge, stigma, depression, and medication adverse effects as contributing to unfavorable treatment outcomes (Gap 4, 86 studies). Medication nonadherence contributed to unfavorable treatment outcomes (Gap 4) and TB recurrence (Gap 5, 14 studies). Limitations include lack of meta-analyses due to the heterogeneity of findings and limited generalizability to some Indian regions, given the country's diverse population., Conclusions: This systematic review illuminates common patterns of risk that shape outcomes for Indians with TB, while highlighting knowledge gaps-particularly regarding TB care for children or in the private sector-to guide future research. Findings may inform targeting of support services to people with TB who have higher risk of poor outcomes and inform multicomponent interventions to close gaps in the care cascade., Competing Interests: MP is an Academic Editor on PLOS Medicine’s editorial board, and serves as Editor-in-Chief of PLOS Global Public Health. MP also serves as an advisor to the following non-profit agencies in global health: Bill & Melinda Gates Foundation; Foundation for Innovative New Diagnostics; World Health Organization & the Stop TB Partnership. JEH has been a paid consultant for Merck. JEH owns stock in Natera. All other authors have declared that no competing interests exist., (Copyright: © 2024 Jhaveri et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Competing Interests: Conflicts of interest; none declared.

Although screening of household contacts (HHCs) of TB patients and provision of TB preventive therapy (TPT) is a key intervention to end the TB epidemic, their implementation globally is dismal. We assessed whether introducing a '7-1-7' timeliness metric was workable for implementing HHC screening among index patients with pulmonary TB diagnosed by private providers in Chennai, India, between November 2022 and March 2023.This was an explanatory mixed-methods study (quantitative-cohort and qualitative-descriptive).There were 263 index patients with 556 HHCs. In 90% of index patients, HHCs were line-listed within 7 days of anti-TB treatment initiation. Screening outcomes were ascertained in 48% of HHCs within 1 day of line-listing. Start of anti-TB treatment, TPT or a decision to receive neither was achieved in 57% of HHC within 7 days of screening. Overall, 24% of screened HHCs in the '7-1-7' period started TPT compared with 16% in a historical control ( P < 0.01). Barriers to achieving '7-1-7' included HHC reluctance for evaluation or TPT, refusal of private providers to prescribe TPT and reliance on facility-based screening of HHCs instead of home visits by health workers for screening.Introduction of a timeliness metric is a workable intervention that adds structure to HHC screening and timely management..

Background: The study assessed whether a "7-1-7" timeliness metric for screening and TB preventive therapy (TPT) could be implemented for household contacts (HHCs) of index patients with bacteriologically confirmed pulmonary TB under routine programmatic settings in Kenya., Methods: A longitudinal cohort study conducted among index patients and their HHCs in 12 health facilities, Kiambu County, Kenya., Results: Between January and June 2023, 95% of 508 index patients had their HHCs line-listed within 7 days of initiating anti-TB treatment ("First 7"). In 68% of 1,115 HHCs, screening outcomes were ascertained within 1 day of line-listing ("Next 1"). In 65% of 1,105 HHCs eligible for further evaluation, anti-TB treatment, TPT or a decision for no drugs was made within 7 days of screening ("Second 7"). Altogether, 62% of screened HHCs started TPT during the "7-1-7" period compared with 58% in a historical cohort. Main barriers to TPT uptake were HHCs not consulting clinicians, HHCs being unwilling to initiate TPT and drug shortages. Healthcare workers felt that a timeliness metric was valuable for streamlining HHC management and proposed "3-5-7" as a workable alternative., Conclusions: The national TB programme must generate awareness about TPT, ensure uninterrupted drug supplies and assess whether the "3-5-7" metric can be operationalised., Competing Interests: Conflicts of interest: none declared., (© 2024 The Authors.)

Introduction: Screening household contacts of TB patients and providing TB preventive therapy (TPT) is a key intervention to end the TB epidemic. Global and timely implementation of TPT in household contacts, however, is dismal. We adapted the 7-1-7 timeliness metric designed to evaluate and respond to infectious disease outbreaks or pandemics, and assessed the feasibility, enablers and challenges of implementing this metric for screening and management of household contacts of index patients with bacteriologically-confirmed pulmonary TB in Karachi city, Pakistan., Methods: We conducted an explanatory mixed methods study with a quantitative component (cohort design) followed by a qualitative component (descriptive design with focus group discussions)., Results: From January-June 2023, 92% of 450 index patients had their household contacts line-listed within seven days of initiating anti-TB treatment ("first 7"). In 84% of 1342 household contacts, screening outcomes were ascertained within one day of line-listing ("next 1"). In 35% of 256 household contacts eligible for further evaluation by a medical officer (aged ≤5 years or with chest symptoms), anti-tuberculosis treatment, TPT or a decision for no drugs was made within seven days of symptom screening ("second 7"). The principal reason for not starting anti-tuberculosis treatment or TPT was failure to consult a medical officer: only 129(50%) of 256 contacts consulted a medical officer. Reasons for poor performance in the "second 7" component included travel costs to see a medical officer, loss of daily earnings and fear of a TB diagnosis. Field staff reported that timeliness metrics motivated them to take prompt action in household contact screening and TPT provision and they suggested these be included in national guidelines., Conclusions: Field staff found "7-1-7" timeliness metrics to be feasible and useful. Integration of these metrics into national guidelines could improve timeliness of diagnosis, treatment and prevention of TB within households of index patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Jamil et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Implementing infection prevention and control (IPC) programmes in line with the World Health Organization's (WHO) eight core components has been challenging in Sierra Leone. In 2021, a baseline study found that IPC compliance in three tertiary hospitals was sub-optimal. We aimed to measure the change in IPC compliance and describe recommended actions at these hospitals in 2023. This was a 'before and after' observational study using two routine cross-sectional assessments of IPC compliance using the WHO IPC Assessment Framework tool. IPC compliance was graded as inadequate (0-200), basic (201-400), intermediate (401-600), and advanced (601-800). The overall compliance scores for each hospital showed an improvement from 'Basic' in 2021 to 'Intermediate' in 2023, with a percentage increase in scores of 16.9%, 18.7%, and 26.9% in these hospitals. There was improved compliance in all core components, with the majority in the 'Intermediate' level for each hospital IPC programme. Recommended actions including the training of healthcare workers and revision of IPC guidelines were undertaken, but a dedicated IPC budget and healthcare-associated infection surveillance remained as gaps in 2023. Operational research is valuable in monitoring and improving IPC programme implementation. To reach the 'Advanced' level, these hospitals should establish a dedicated IPC budget and develop long-term implementation plans.

Many patients with tuberculosis (TB) have comorbidities, risk determinants and disability that co-exist at diagnosis, during and after TB treatment. We conducted an observational cohort study in 11 health facilities in China to assess under routine program conditions (i) the burden of these problems at the start and end of TB treatment and (ii) whether referral mechanisms for further care were functional. There were 603 patients registered with drug-susceptible TB who started TB treatment: 84% were symptomatic, 14% had diabetes, 14% had high blood pressure, 19% smoked cigarettes, 10% drank excess alcohol and in 45% the 6 min walking test (6MWT) was abnormal. Five patients were identified with mental health disorders. There were 586 (97%) patients who successfully completed TB treatment six months later. Of these, 18% were still symptomatic, 12% had diabetes (the remainder with diabetes failed to complete treatment), 5% had high blood pressure, 5% smoked cigarettes, 1% drank excess alcohol and 25% had an abnormal 6MWT. Referral mechanisms for the care of comorbidities and determinants worked well except for mental health and pulmonary rehabilitation for disability. There is need for more programmatic-related studies in other countries to build the evidence base for care of TB-related conditions and disability.

Until 2021, in the Kyrgyz Republic, tuberculosis (TB) was diagnosed and treated only in the public sector. With funding support of the STOP-TB partnership, the private providers in four regions of the country and Bishkek city were mapped, trained and incentivized to screen for and identify presumptive TB patients and refer them to the public facilities for diagnosis and treatment. In this study, we describe the cascade of care of such patients. This was a cohort study involving secondary analysis of routine data. Of 79,352 patients screened during February 2021-March 2022, 2511 (3%) had presumptive TB, of whom 903 (36%) were not tested for TB [pre-diagnostic loss to follow-up]. A total of 323 (13%) patients were diagnosed with TB, of whom, 42 (13%) were not started on treatment [pre-treatment loss to follow-up]. Among 257 patients eligible for outcome assessment, 197 (77%) had treatment success, 29 (11%) were lost-to-follow-up, 13 (5%) died, 4 (2%) had treatment failure and 14 (5%) were not evaluated. While this donor-funded, pioneering initiative was successful in engaging the private sector, we recommend that the national TB programme scales up the initiative nationally with dedicated budgets, activities and plans to monitor progress. Qualitative research is urgently needed to understand the reasons for the gaps in the care cascade.

Objectives: To determine the proportion of Salmonella enterica in fecal samples of live pigs with suspected salmonellosis analyzed at the diagnostic unit of the University of Antioquia, Colombia between 2019 and 2021, and examine the serotypes and antimicrobial resistance patterns., Methods: This was a laboratory-based cross-sectional study of routine data on fecal samples received from pig farms in all nine subregions of Antioquia state, Colombia. Salmonella spp. detection at the university is done using enrichment, selective culture, and polymerase chain reaction. Serotypes were identified using the Kauffmann-White scheme and isolates were tested for antimicrobial susceptibility using broth microdilution., Results: Of 653 samples tested, 149 (23%) were positive for S. enterica. Nine serotypes were identified. The most common were Salmonella Typhimurium (56%) and its monophasic variant (35%). Resistance to ampicillin (70%) was most frequently observed, followed by ciprofloxacin (55%), and sulfamethoxazole-trimethoprim (52%). No isolates were resistant to amikacin and gentamicin. Multidrug resistance (resistance to ≥ 3 classes of antibiotics) was observed in 61 (44%) isolates. Multidrug resistance was highest in S. Typhimurium (57%) compared with the other serotypes. Serotype was associated with multidrug resistance ( p = 0.01), but age of the pig and sub-region were not., Conclusions: The proportion of Salmonella spp. and the associated high levels of multidrug resistance are of concern and may indicate irrational use of antimicrobials and poor management practices in pig production systems in the region. Strengthened surveillance is needed to monitor and improve farm management practices and the use of antimicrobials in farms in Colombia.

The registration of individuals with designated primary medical care institutions (PMCIs) is a key step towards their empanelment with these PMCIs, supported by the Primary Health Care System Strengthening Project in Sri Lanka. We conducted an explanatory mixed-methods study to assess the extent of registration at nine selected PMCIs and understand the challenges therein. By June 2021, 36,999 (19.2%, 95% CI-19.0-19.4%) of the 192,358 catchment population allotted to these PMCIs were registered. At this rate, only 50% coverage would be achieved by the end of the project (December 2023). Proportions of those aged <35 years and males among those registered were lower compared to their general population distribution. Awareness activities regarding registration were conducted in most of the PMCIs, but awareness in the community was low. Poor registration coverage was due to a lack of dedicated staff for registration, misconceptions of health care workers about individuals needing to be registered, reliance on opportunistic or passive registration, and lack of monitoring mechanisms; these were further compounded by the COVID-19 pandemic. Moving forward, there is an urgent need to address these challenges to improve registration coverage and ensure that all individuals are empaneled before the close of the project for it to have a meaningful impact.

The Primary Healthcare System Strengthening Project in Sri Lanka focuses on improving noncommunicable disease (NCD) care provision at primary medical care institutions (PMCIs). We conducted an explanatory mixed-methods study to assess completeness of screening for NCD risk, linkage to care, and outcomes of diabetes/hypertension care at nine selected PMCIs, as well as to understand reasons for gaps. Against a screening coverage target of 50% among individuals aged ≥ 35 years, PMCIs achieved 23.3% (95% CI: 23.0-23.6%) because of a lack of perceived need for screening among the public and COVID-19-related service disruptions. Results of investigations and details of further referral were not documented in almost half of those screened. Post screening, 45% of those eligible for follow-up NCD care were registered at medical clinics. Lack of robust recording/tracking mechanisms and preference for private providers contributed to post-screening attrition. Follow-up biochemical investigations for monitoring complications were not conducted in more than 50% of diabetes/hypertension patients due to nonprescription of investigations by healthcare providers and poor uptake among patients because of nonavailability of investigations at PMCI, requiring them to avail services from the private sector, incurring out-of-pocket expenditure. Primary care strengthening needs to address these challenges to ensure successful integration of NCD care within PMCIs.

Background: Hepatitis C virus (HCV) and hepatitis B virus (HBV) coinfection are associated with increased mortality in people with HIV (PWH), and hyperglycemia is a common comorbidity in PWH. In this study, we used routinely collected clinical data to assess the associations between HBV and HCV seropositivity with all-cause mortality and whether this relationship differs by hyperglycemia status., Methods: Eligible participants included adult PWH (≥15 years) who initiated antiretroviral therapy between May 2005 and June 2016 in Myanmar. HBV and HCV serostatus and hyperglycemia were measured at enrollment to HIV care using HBV surface antigen, HCV antibody tests, and random blood glucose (≥140 mg/dL), respectively., Results: Among 27 722 PWH, 2260 (8%) were HBV seropositive, 2265 (9%) were HCV seropositive, 178 (0.6%) were HBV-HCV seropositive, and 1425 (5%) had hyperglycemia. During the median follow-up (interquartile range) of 3.1 (1.5-5.1) years, 3655 (13%) PWH died, and the overall mortality rate was 3.8 (95% CI, 3.7-3.9) per 100-person-years (PY). The mortality rate (per 100 PY) among PWH who were HBV seropositive was 4.6, among PWH who were HCV seropositive it was 5.1, and among PWH who were HBV-HCV seropositive it was 7.1. When stratified by glycemic status, the mortality rate was higher among patients with hyperglycemia compared with those with euglycemia (5.4 vs 4.0 per 100 PY), and the difference in mortality rate between patients with hyperglycemia and euglycemia was highest among those with HCV seropositivity (9.8 vs 5.0 per 100 PY)., Conclusions: Increased mortality rates associated with HBV and HCV seropositivity in PWH differed by their glycemic status. PWH with HCV seropositivity and hyperglycemia had the highest mortality rates., Competing Interests: Potential conflicts of interest. All authors: no reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: National tuberculosis (TB) programmes in high-burden countries do not systematically assess severity at diagnosis followed by referral for inpatient care. Due to limited capacity, comprehensive assessment of all TB patients is not practical. In three districts of Gujarat (West India) in June 2021, we determined the feasibility of screening for severe illness by paramedical staff of public facilities and the burden of 'high risk for severe illness' at notification among adults (≥15 y of age) with TB., Methods: In this cross-sectional study, the screening criteria for high risk for severe illness was the presence of any one of the following: body mass index (BMI) ≤14.0 kg/m2, BMI ≤16.0 kg/m2 with bilateral leg swelling, respiratory rate >24/min, oxygen saturation <94% or inability to stand without support. We summarized the feasibility indicators and burden using proportion (95% confidence interval [CI]) and median, as applicable., Results: Of 626 notified adults, 87% were screened. The median time interval for screening was 3 d from notification and all indicators were collected in 97% of patients. The burden of high risk for severe illness was high, at 41.6% (95% CI 37.5 to 45.8)., Conclusions: High burden and feasibility (high coverage, acceptable time interval and minimal missing data) makes a strong case for routine screening of severe illness., (© The Author(s) 2022. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Like the world over, Nepal was also hard hit by the second wave of COVID-19. We audited the clinical care provided to COVID-19 patients admitted from April to June 2021 in a tertiary care hospital of Nepal. This was a cohort study using routinely collected hospital data. There were 620 patients, and most (458, 74%) had severe illness. The majority (600, 97%) of the patients were eligible for admission as per national guidelines. Laboratory tests helping to predict the outcome of COVID-19, such as D-dimer and C-reactive protein, were missing in about 25% of patients. Nearly all (>95%) patients with severe disease received corticosteroids, anticoagulants and oxygen. The use of remdesivir was low (22%). About 70% of the patients received antibiotics. Hospital exit outcomes of most (>95%) patients with mild and moderate illness were favorable (alive and discharged). Among patients with severe illness, about 25% died and 4% were critically ill, needing further referral. This is the first study from Nepal to audit and document COVID-19 clinical care provision in a tertiary care hospital, thus filling the evidence gap in this area from resource-limited settings. Adherence to admission guidelines was excellent. Laboratory testing, access to essential drugs and data management needs to be improved.

A Primary Healthcare-System-Strengthening Project (PSSP) is implemented by the Ministry of Health, Sri Lanka, with funding support from the World Bank for providing quality care through primary medical care institutions (PMCIs). We used an explanatory mixed-methods study to assess progress and challenges in human resources, drug availability, laboratory services and the health management information system (HMIS) at PMCIs. We conducted a checklist-based assessment followed by in-depth interviews of healthcare workers in one PMCI each in all nine provinces. All PMCIs had medical/nursing officers, but data entry operators (44%) and laboratory technicians (33%) were mostly not available. Existing staff were assigned additional responsibilities in PSSP, decreasing their motivation and efficiency. While 11/18 (61%) essential drugs were available in all PMCIs, buffer stocks were not maintained in >50% due to poor supply chain management and storage infrastructure. Only 6/14 (43%) essential laboratory investigations were available in >50% of PMCIs, non-availability was due to shortages of reagents/consumables and lack of sample collection−transportation system. The HMIS was installed in PMCIs but its usage was sub-optimal due to perceived lack of utility, few trained operators and poor internet connectivity. The PSSP needs to address these bottlenecks as a priority to ensure sustainability and successful scale-up.

Introduction : Qualitative studies are often inadequately reported, making it difficult to judge their appropriateness for decision making in public health. We assessed the publication characteristics and quality of reporting of qualitative and mixed-method studies from the Structured Operational Research and Training Initiative (SORT IT), a global partnership for operational research capacity building. Methods: A cross-sectional analysis of publications to assess the qualitative component using an adapted version of the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist. Results: In 67 publications involving 18 countries, 32 journals and 13 public health themes, 55 were mixed-methods studies and 12 were qualitative studies. First authorship from low-and-middle-income (LMIC) countries was present in 64 (96%), LMIC last authorship in 55 (82%), and female first authorship in 30 (45%). The mean LMIC institutions represented per publication was five (range 1-11). Sixty-three (94%) publications were open access. Reporting quality was graded as 'good' to 'excellent' in 60 (89%) publications, 'fair' in five (8%) and 'poor' in two (3%). Conclusion: Most SORT IT publications adhered to COREQ standards, while supporting gender equity in authorship and the promotion of LMIC research leadership. SORT IT plays an important role in ensuring quality of evidence for decision making to improve public health.

Nasopharyngeal carriage of aerobic Gram-negative bacilli (GNB) may precede the development of invasive respiratory infections. We assessed the prevalence of nasopharyngeal carriage of aerobic GNB and their antimicrobial resistance patterns among healthy under-five children attending seven selected day-care centres in the Accra metropolis of the Greater Accra region of Ghana from September to December 2016. This cross-sectional study analysed a total of 410 frozen nasopharyngeal samples for GNB and antimicrobial drug resistance. The GNB prevalence was 13.9% (95% CI: 10.8-17.6%). The most common GNB were Escherichia coli (26.3%), Klebsiella pneumoniae (24.6%), and Enterobacter cloacae (17.5%). Resistance was most frequent for cefuroxime (73.7%), ampicillin (64.9%), and amoxicillin/clavulanic acid (59.6%). The organisms were least resistant to gentamicin (7.0%), amikacin (8.8%), and meropenem (8.8%). Multidrug resistance (MDR, being resistant to ≥3 classes of antibiotics) was observed in 66.7% (95% CI: 53.3-77.8%). Extended-spectrum beta-lactamase (ESBL)-producing bacteria constituted 17.5% (95% CI: 9.5-29.9%), AmpC-producing bacteria constituted 42.1% (95% CI: 29.8-55.5%), and carbapenemase-producing bacteria constituted 10.5% (95% CI: 4.7-21.8%) of isolates. The high levels of MDR are of great concern. These findings are useful in informing the choice of antibiotics in empiric treatment of GNB infections and call for improved infection control in day-care centres to prevent further transmission.

Due to the coronavirus disease (COVID-19) pandemic and its associated response, TB deaths increased for the first time in a decade. In any potentially fatal illness, an assessment of severity is essential. This is not systematically done for adults with TB, mostly due to a lack of policy and/or limited availability of diagnostic and clinical capacity. We developed a screening tool using simple and easily measurable indicators that can be used by paramedical TB program staff to quickly identify people with severe illness. During October-November 2020 in Karnataka, India, the paramedical program staff from 16 districts screened people with TB (aged ≥15 years) notified by public facilities for "high risk of severe illness," which was defined as the presence of any of the following indicators: (1) body mass index (BMI) ≤14.0 kg/m 2 ; (2) BMI ≤16.0 kg/m 2 with bilateral leg swelling; (3) respiratory rate >24/minute; (4) oxygen saturation <94%; (5) inability to stand without support. In this cohort study, we determined the incidence of program-recorded early deaths (within 2 months) and its association with high risk of severe illness. Of 3,010 people with TB, 1,529 (50.8%) were screened at diagnosis/notification, of whom 537 (35.1%) had a high risk of severe illness. There were 195 (6.5%, 95% CI=5.7, 7.4) early deaths: 59 (30.2%) within a week and 100 (51.3%) within 2 weeks of treatment initiation. The incidence of early deaths was significantly higher among those with high risk of severe illness (8.9%) at diagnosis compared to those without (3.8%) [adjusted relative risk: 2.36 (95% confidence interval=1.57, 3.55)]. To conclude, early deaths were especially high during the first 2 weeks and strongly associated with a high risk of severe illness at diagnosis/notification. Screening for severe illness should be explored as a potential strategy to end TB deaths., (© Shewade et al.)

The COVID-19 pandemic and public health response to the pandemic has caused huge setbacks in the management of other infectious diseases. In the present study, we aimed to (i) assess the trends in numbers of samples from patients with influenza-like illness and severe acute respiratory syndrome tested for influenza and the number and proportion of cases detected from 2015−2021 and (ii) examine if there were changes during the COVID-19 period (2020−2021) compared to the pre-COVID-19 period (2015−2019) in three states of India. The median (IQR) number of samples tested per month during the pre-COVID-19 period was 653 (395−1245), compared to 27 (11−98) during the COVID-19 period (p value < 0.001). The median (IQR) number of influenza cases detected per month during the pre-COVID-19 period was 190 (113−372), compared to 29 (27−30) during the COVID-19 period (p value < 0.001). Interrupted time series analysis (adjusting for seasonality and testing charges) confirmed a significant reduction in the total number of samples tested and influenza cases detected during the COVID-19 period. However, there was no change in the influenza positivity rate between pre-COVID-19 (29%) and COVID-19 (30%) period. These findings suggest that COVID-19-related disruptions, poor health-seeking behavior, and overburdened health systems might have led to a reduction in reported influenza cases rather than a true reduction in disease transmission.

The transfer of antibiotic resistance from animals to humans is of concern in recent times. One potential source of such transfer is the untreated poultry excreta used as manure in farming. We aim to identify bacterial isolates and antibiotic susceptibility patterns of Escherichia coli in poultry excreta in Sierra Leone. This was a cross-sectional study of fresh poultry excreta samples collected from four commercial poultry sites in Freetown, Sierra Leone, from June−September 2021. Bacterial isolates were tested against eight antibiotics using established standards. Of 100 samples, 93 showed Escherichia coli (93%): of those, eight isolates also had Salmonella (8%). E. coli was 100% resistant to all three ‘Watch’ drugs (erythromycin, cefoxitin and streptomycin) and tetracycline. E. coli was least resistant to ampicillin (12%), followed by chloramphenicol (35%). The prevalence of multidrug resistance was 95.6%. Multiple antibiotic resistance index ranged from 0.5−0.7 (optimal < 0.2), indicating high prior exposure to antibiotics in these poultries. Such high levels of resistance in E. coli isolated from poultry excreta could pose a serious threat to humans. We recommend (i) routine surveillance to monitor antibiotic resistance in poultry excreta, (ii) using poultry excreta as manure only after treatment and (iii) restricting the use of antibiotics as prophylactics and growth promoters in poultry feeds.

Infection Prevention and Control (IPC) measures are critical to the reduction in healthcare-associated infections, especially during pandemics, such as that of COVID-19. We conducted a hospital-based cross-sectional study in August 2021 at Connaught Hospital, Princess Christian Maternity Hospital and Ola During Children's Hospital located in Freetown, Sierra Leone. We used the World Health Organization's Infection Prevention and Control Assessment Framework Tool to assess the level of IPC compliance at these healthcare facilities. The overall IPC compliance score at Connaught Hospital was 323.5 of 800 points, 313.5 of 800 at Ola During Children's Hospital, 281 of 800 at Princess Christian Maternity Hospital, implying a 'Basic' IPC compliance grade. These facilities had an IPC program, IPC committees and dedicated IPC focal persons. However, there were several challenges, including access to safe and clean water and insufficient quantities of face masks, examination gloves and aprons. Furthermore, there was no dedicated budget or no healthcare-associated infection (HAI) surveillance, and monitoring/audit of IPC practices were weak. These findings are of concern during the COVID-19 era, and there is an urgent need for both financial and technical support to address the gaps and challenges identified.

Inappropriate use of antibiotics during the COVID-19 pandemic has the potential to increase the burden of antimicrobial resistance. In this study, we report on the prevalence of antibiotic use and its associated factors among suspected and confirmed COVID-19 patients admitted to 35 health facilities in Sierra Leone from March 2020-March 2021. This was a cross-sectional study using routinely collected patient data. Of 700 confirmed COVID-19 patients, 47% received antibiotics. The majority (73%) of the antibiotics belonged to the 'WATCH' group of antibiotics, which are highly toxic and prone to resistance. The most frequently prescribed antibiotics were azithromycin, ceftriaxone, amoxicillin, metronidazole, and amoxicillin-clavulanic acid. Antibiotic use was significantly higher in patients aged 25-34 years than in those with severe disease. Of 755 suspected COVID-19 patients, 61% received antibiotics, of which the majority (58%) belonged to the 'WATCH' category. The most frequently prescribed antibiotics were ceftriaxone, metronidazole, azithromycin, ciprofloxacin, and amoxycillin. The prevalence of antibiotic use among suspected and confirmed COVID-19 patients admitted to healthcare facilities in Sierra Leone was high and not in line with national and WHO case management guidelines. Training of health care providers, strengthening of antimicrobial stewardship programs, and microbiological laboratory capacity are urgently needed.

Background: India implements universal drug susceptibility testing (UDST) using rapid genotypic tests (cartridge-based nucleic acid amplification test CBNAAT - and line probe assay - LPA). to bridge the gap of diagnosis of multidrug/rifampicin-resistant TB. There is limited evidence assessing the implementation of UDST in India. We assessed the implementation among people with pulmonary TB notified from public facilities in October 2019 from Raichur (Karnataka), India., Methods: A cohort study involving secondary data in routine programme settings was conducted. All people with TB underwent a rapid genotypic DST for rifampicin resistance followed by first line-LPA (FL-LPA) if sensitive and second line-LPA (SL-LPA) if resistant., Results: Of 217 people, 15.7% (n=34) did not undergo rapid genotypic DST. Of 135 who were rifampicin-sensitive detected on CBNAAT, 68.1% (n=92) underwent FL-LPA, and out of the six rifampicin-resistant cases, 66.7% (n=4) underwent SL-LPA. Overall, 65.4% (142/217) completed the UDST algorithm. Children (aged <15 y) and people with bacteriological non-confirmation on microscopy were less likely to undergo rapid genotypic DST. Of 183 patients who underwent both rapid genotypic DST and sputum smear microscopy, 150 were bacteriologically confirmed and, of them, 9 (6%) were 'rapid DST-negative'., Conclusion: We found gaps at various steps. There were a significant number of 'rapid DST-negative, smear-positive' patients., (© The Author(s) 2021. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Objectives: Low BMI and hyperglycemia are each important risk factors for tuberculosis (TB). However, the contribution of synergy between low BMI and hyperglycemia to risk of TB among people living with HIV (PWH) is unexplored. We compared TB incidence among PWH with different exposure profiles to low BMI (BMI < 18.5 kg/m2) and hyperglycemia (random blood glucose ≥140 mg/dl)., Design and Methods: We conducted a cohort study using data of PWH (≥15 years) who enrolled in Myanmar's Integrated HIV Care Program between 2011 and 2017. We used their follow-up data until 2018 to determine TB incidence., Results: Among 20 865 PWH included in this study, 7610 (36%) had low BMI only, 1324 (6%) had hyperglycemia only, and 465 (2%) patients had concurrent low BMI and hyperglycemia (joint exposure) at baseline. During a median follow-up of 2.2 years (interquartile range: 0.5, 4.2), 3628 (17%) developed TB [6.7, 95% confidence interval (CI): 6.5,7.0 cases per 100 person-years (PY)]. TB incidence among PWH with joint exposure was 21.0 (95% CI: 18.0, 24.7), with low BMI only was 10.9 (95% CI: 10.4, 11.4), with hyperglycemia only was 5.2 (95% CI: 4.4, 6.3) and with no exposure was 4.6 (95% CI: 4.4, 4.9) cases per 100 PY. The attributable proportion of incident TB due to synergy between low BMI and hyperglycemia was 0.23 (95% CI: 0.06, 0.36)., Conclusion: Synergy between low BMI and hyperglycemia was associated with increased excess TB incidence in PWH. TB preventive treatment, nutritional support, and hyperglycemia management should be evaluated as interventions to reduce TB risk in PWH with joint exposure., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Tuberculosis (TB) remains a public health burden in the Republic of Karakalpakstan, Uzbekistan. This region-wide retrospective cohort study reports the treatment outcomes of patients registered in the TB electronic register and treated with first-line drugs in the TB Programme of the Republic of Karakalpakstan from 2005-2020 and factors associated with unfavourable outcomes. Among 35,122 registered patients, 24,394 (69%) patients were adults, 2339 (7%) were children, 18,032 (51%) were male and 19,774 (68%) lived in rural areas. Of these patients, 29,130 (83%) had pulmonary TB and 7497 (>22%) had been previously treated. There were 7440 (21%) patients who had unfavourable treatment outcomes. Factors associated with unfavourable treatment outcomes included: increasing age, living in certain parts of the republic, disability, pensioner status, unemployment, being HIV-positive, having pulmonary TB, and receiving category II treatment. Factors associated with death included: being adult and elderly, living in certain parts of the republic, having a disability, pensioner status, being HIV-positive, and receiving category II treatment. Factors associated with failure included: being adolescent, female, having pulmonary TB. Factors associated with loss to follow-up included: being male, disability, pensioner status, unemployment, receiving category II treatment. In summary, there are sub-groups of patients who need special attention in order to decrease unfavourable treatment outcomes.

Setting: There are concerns about the occurrence of multidrug resistance (MDR) in patients with urine tract infections (UTI) in Nepal., Objective: To determine culture positivity, trends in MDR among Escherichia coli and Klebsiella pneumoniae infections and seasonal changes in culture-positive UTI specimens isolated from 2014 to 2018 at the B P Koirala Institute of Health Sciences, Dharan, Eastern Nepal., Design: This was a cross-sectional study using secondary laboratory data., Results: Among 116,417 urine samples tested, 19,671 (16.9%) were culture-positive, with an increasing trend in the number of samples tested and culture positivity. E. coli was the most common bacteria (54.3%), followed by K. pneumoniae (8.8%). Among E. coli and K. pneumoniae isolates, MDR was found in respectively 42.5% and 36.0%. MDR was higher in males and people aged >55 years, but showed a decreasing trend over the years. The numbers of isolates increased over the years, with a peak always observed from July to August., Conclusion: Low culture positivity is worrying and requires further work into improving diagnostic protocols. Decreasing trends in MDR are a welcome sign. Information on seasonal changes that peak in July-August can help laboratories better prepare for this time with adequate buffer stocks to ensure culture and antibiotic susceptibility testing., Competing Interests: Conflict of interests: none declared., (© 2021 The Union.)

Setting: Nine drug-resistant TB centres, some of them supported by Damien Foundation in Nepal where >80% of multidrug-resistant/rifampicin-resistant TB (MDR/RR-TB) patients are treated., Objective: To assess the uptake, effectiveness and safety of the 9-12-month shorter treatment regimen (STR) in MDR/RR-TB patients registered from January 2018 to December 2019., Design: This was a cohort study involving secondary programme data., Results: Of 631 patients, 301 (48.0%) started and continued STR. Key reasons for ineligibility to start/continue STR were baseline resistance or exposure to second-line drugs (62.0%), contact with extensively drug-resistant TB (XDR-TB) or pre-XDR-TB (7.0%) patients and unavailability of STR drugs (6.0%). Treatment success was 79.6%; unsuccessful outcomes were death (12.0%), lost to follow-up (5.3%), failure (2.7%) and not evaluated (0.7%). Unsuccessful outcomes were significantly associated with HIV positivity and patient age ⩾55 years, with adjusted relative risk of respectively 2.39 (95% CI 1.52-3.77) and 3.86 (95% CI 2.30-6.46). Post-treatment recurrence at 6 and 12 months was respectively 0.5% and 2.4%. Serious adverse events (SAEs) were seen in 15.3% patients - hepatotoxicity and ototoxicity were most common., Conclusion: STR had a modest uptake, high treatment success and low post-treatment recurrence. For proper detection and management of SAEs, improving pharmacovigilance might be considered. Availability of rapid diagnostic test for second-line drugs is crucial for correct patient management., Competing Interests: Conflict of interests: none declared., (© 2021 The Union.)

To understand how insect pollinators find flowers against complex backgrounds in diverse natural habitats, it is required to accurately estimate the thresholds for target detection. Detection thresholds for single targets vary between bee species and have been estimated in the Western honeybee, a species of bumblebee and in a stingless bee species. We estimated the angular range of detection for coloured targets in the Asian honeybee Apis cerana. Using a Y-maze experimental set up, we show that targets that provided both chromatic and green receptor contrast were detected at a minimum visual angle of 7.7°, while targets with only chromatic contrast were detected at a minimum angle of 13.2°. Our results thus provide a robust foundation for future studies on the visual ecology of bees in a comparative interspecific framework.

Due to limited availability of diagnostics and capacity, people with tuberculosis do not always undergo systematic assessment for severe illness (requiring inpatient care). In Karnataka (south India), para-medical programme staff used a screening tool to identify people at 'high risk of severe illness', defined using indicators of very severe undernutrition, abnormal vital signs and poor performance status (any one): (i) body mass index (BMI) ≤ 14.0 kg/m 2 (ii) BMI ≤ 16.0 kg/m 2 with bilateral leg swelling (iii) respiratory rate > 24/min (iv) oxygen saturation < 94% (v) inability to stand without support. Of 3020 adults notified from public facilities (15 October to 30 November 2020) in 16 districts, 1531 (51%) were screened (district-wise range: 13-90%) and of them, 538 (35%) were classified as 'high risk of severe illness'. Short median delays in screening from notification (five days), and all five indicators being collected for 88% of patients, suggests the feasibility of using this tool in programme settings. However, districts with poor screening coverage require further attention. To end tuberculosis deaths, screening should be followed by referral to higher facilities for comprehensive clinical evaluation, to assess the need for inpatient care. Future studies should assess the validity (especially sensitivity in picking severely ill patients) of this screening tool.

Real-time operational research can be defined as research on strategies or interventions to assess if they are feasible, working as planned, scalable and effective. The research involves primary data collection, periodic analysis during the conduct of the study and dissemination of the findings to policy makers for timely action. This paper aims to illustrate the use of real-time operational research and discuss how to make it happen. Four case studies are presented from the field of tuberculosis. These include (i) mis-registration of recurrent tuberculosis in Malawi; (ii) HIV testing and adjunctive cotrimoxazole to reduce mortality in TB patients in Malawi; (iii) screening TB patients for diabetes mellitus in India; and (iv) mitigating the impact of COVID-19 on TB case detection in capital cities in Kenya, Malawi and Zimbabwe. The important ingredients of real-time operational research are sound ethics; relevant research; adherence to international standards of conducting and reporting on research; consideration of comparison groups; timely data collection; dissemination to key stakeholders; capacity building; and funding. Operational research can improve the delivery of established health interventions and ensure the deployment of new interventions as they become available, irrespective of diseases. This is particularly important when public health emergencies, including pandemics, threaten health services.

In 2019, global diabetes prevalence was 463 million. Diabetes increases the risk of TB and adverse treatment outcomes including death and relapse. Diabetes also increases the risk of severe disease, multi-organ failure, coagulopathy and death in COVID-19. TB and COVID-19 share many features, suggesting opportunities to integrate prevention, diagnosis and care. Three areas for further work are highlighted: better infection control in diabetes clinics, easier and quicker diagnosis using similar technology platforms and optimal blood glucose control. The funding and resources for COVID-19 should be harnessed to improve TB and diabetes care and achieve their respective sustainable development goal targets., (© The Author(s) 2021. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

When COVID-19 was declared a pandemic, there was concern that TB and HIV services in Zimbabwe would be severely affected. We set up real-time monthly surveillance of TB and HIV activities in 10 health facilities in Harare to capture trends in TB case detection, TB treatment outcomes and HIV testing and use these data to facilitate corrective action. Aggregate data were collected monthly during the COVID-19 period (March 2020-February 2021) using EpiCollect5 and compared with monthly data extracted for the pre-COVID-19 period (March 2019-February 2020). Monthly reports were sent to program directors. During the COVID-19 period, there was a decrease in persons with presumptive pulmonary TB (40.6%), in patients registered for TB treatment (33.7%) and in individuals tested for HIV (62.8%). The HIV testing decline improved in the second 6 months of the COVID-19 period. However, TB case finding deteriorated further, associated with expiry of diagnostic reagents. During the COVID-19 period, TB treatment success decreased from 80.9 to 69.3%, and referral of HIV-positive persons to antiretroviral therapy decreased from 95.7 to 91.7%. Declining trends in TB and HIV case detection and TB treatment outcomes were not fully redressed despite real-time monthly surveillance. More support is needed to transform this useful information into action.

When the COVID-19 pandemic was announced in March 2020, there was concern that TB and HIV programme services in Malawi would be severely affected. We set up real-time monthly surveillance of TB and HIV activities in eight health facilities in Lilongwe to see if it was possible to counteract the anticipated negative impact on TB case detection and treatment and HIV testing. Aggregate data were collected monthly during the COVID-19 period (March 2020-February 2021) using an EpiCollect5 application and compared with monthly data collected during the pre-COVID-19 period (March 2019-February 2020); these reports were sent monthly to programme directors. During COVID-19, there was an overall decrease in persons presenting with presumptive pulmonary TB (45.6%), in patients registered for TB treatment (19.1%), and in individuals tested for HIV (39.0%). For presumptive TB, children and females were more affected, but for HIV testing, adults and males were more affected. During COVID-19, the TB treatment success rate (96.1% in pre-COVID-19 and 96.0% during COVID-19 period) and referral of HIV-positive persons to antiretroviral therapy (100% in pre-COVID-19 and 98.6% during COVID-19 period) remained high and largely unchanged. Declining trends in TB and HIV case detection were not redressed despite real-time monthly surveillance.

Wound infections with drug-resistant bacteria lead to higher mortality and morbidity and increased healthcare costs. We aimed to describe the spectrum of bacterial pathogens, isolated from wound cultures in Yangon General Hospital in 2018, and their antimicrobial resistance (AMR) patterns and to understand the challenges in implementing an AMR surveillance system in Myanmar. We conducted a concurrent mixed-methods study involving analysis of surveillance data and in-depth interviews with nine key personnel involved in AMR surveillance. Of 1418 wound specimens processed, 822 (58%) were culture-positive. The most common Gram-positive bacteria were coagulase-negative staphylococci (23.3%) and Staphylococcus aureus (15.1%). Among Gram-negative bacteria, Escherichia coli (12.5%) and Pseudomonas aeruginosa (10.1%) were common. Staphylococcus aureus isolates were resistant to penicillin (98%), oxacillin (70%) and tetracycline (66%). Escherichia coli showed resistance to ampicillin (98%). Lack of dedicated and trained staff (microbiologist, technician, data entry operator), lack of computers at sentinel sites and non-uniform and non-standardized data capture formats were the major challenges in implementing AMR surveillance. These challenges need to be addressed urgently. We also recommend periodic analysis and sharing of antibiograms at every hospital to inform the treatment regimens used in wound management.

Antimicrobials help in the prevention and treatment of infections and are crucial for animal production, but overuse can result in antimicrobial resistance. Hence, understanding data quality on livestock antimicrobial use is essential. We assessed frequency of reporting, completeness, and concordance of reported data and availability of human resources and infrastructure in 14 districts in Sierra Leone. This was a cross-sectional study involving a review of district and sub-district animal treatment forms submitted from January 2016 to August 2019. Out of the 14 districts, only 3 had filled forms available for review: A total of 6 (0.97% of 616 expected) district forms and 79 (1.15% of 6840 expected) sub-district forms. Data between district and sub-district treatment forms were fully discordant. Hence, completeness of data could not be assessed. All districts had livestock officers (barring one) and livestock assistants but no veterinarians. The gap in community animal health workers ranged from 14 to 100% per district. No districts had a functional computer or internet access. Reporting was non-existent in 11 districts and poor in the other 3. Resources are urgently needed to address critical gaps in human resources and capacity and computer and Internet connectivity to develop critical One Health surveillance functions at the national and sub-national levels.

There was concern that the COVID-19 pandemic would adversely affect TB and HIV programme services in Kenya. We set up real-time monthly surveillance of TB and HIV activities in 18 health facilities in Nairobi so that interventions could be implemented to counteract anticipated declining trends. Aggregate data were collected and reported monthly to programme heads during the COVID-19 period (March 2020-February 2021) using EpiCollect5 and compared with monthly data collected during the pre-COVID period (March 2019-February 2020). During the COVID-19 period, there was an overall decrease in people with presumptive pulmonary TB (31.2%), diagnosed and registered with TB (28.0%) and in those tested for HIV (50.5%). Interventions to improve TB case detection and HIV testing were implemented from August 2020 and were associated with improvements in all parameters during the second six months of the COVID-19 period. During the COVID-19 period, there were small increases in TB treatment success (65.0% to 67.0%) and referral of HIV-positive persons to antiretroviral therapy (91.2% to 92.9%): this was more apparent in the second six months after interventions were implemented. Programmatic interventions were associated with improved case detection and treatment outcomes during the COVID-19 period, suggesting that monthly real-time surveillance is useful during unprecedented events.

Globally, 5-15% of hospitalized patients acquire infections (often caused by antimicrobial-resistant microbes) due to inadequate infection prevention and control (IPC) measures. We used the World Health Organization's (WHO) 'Infection Prevention and Control Assessment Framework' (IPCAF) tool to assess the IPC compliance at Lira University hospital (LUH), a teaching hospital in Uganda. We also characterized challenges in completing the tool. This was a hospital-based, cross-sectional study conducted in November 2020. The IPC focal person at LUH completed the WHO IPCAF tool. Responses were validated, scored, and interpreted per WHO guidelines. The overall IPC compliance score at LUH was 225/800 (28.5%), implying a basic IPC compliance level. There was no IPC committee, no IPC team, and no budgets. Training was rarely or never conducted. There was no surveillance system and no monitoring/audit of IPC activities. Bed capacity, water, electricity, and disposal of hospital waste were adequate. Disposables and personal protective equipment were not available in appropriate quantities. Major challenges in completing the IPCAF tool were related to the detailed questions requiring repeated consultation with other hospital stakeholders and the long time it took to complete the tool. IPC compliance at LUH was not optimal. The gaps identified need to be addressed urgently.

Background: Pakistan implemented initiatives to detect tuberculosis (TB) patients through extended contact screening (ECS); it improved case detection but treatment outcomes need assessment., Objectives: To compare treatment outcomes of pulmonary TB (PTB) patients detected by ECS with those detected by routine passive case finding (PCF)., Methods: A cohort study using secondary program data conducted in Lahore, Faisalabad and Rawalpindi districts and Islamabad in 2013-15. We used log binomial regression models to assess if ECS was associated with unfavorable treatment outcomes (death, loss-to-follow-up, failure, not evaluated) after adjusting for potential confounders., Results: We included 79,431 people with PTB; 4604 (5.8%) were detected by ECS with 4052 (88%) bacteriologically confirmed. In all PTB patients the proportion with unfavorable outcomes was not significantly different in ECS group (9.6%) compared to PCF (9.9%), however, among bacteriologically confirmed patients unfavorable outcomes were significantly lower in ECS (9.9%) than PCF group (11.6%, P = 0.001). ECS was associated with a lower risk of unfavorable outcomes (adjusted relative risk (aRR) 0.90; 95% CI 0.82-0.99) among 'all PTB' patients and bacteriologically confirmed PTB patients (aRR 0.91; 95% CI 0.82-1.00)., Conclusion: In PTB patients detected by ECS the treatment outcomes were not inferior to those detected by PCF., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

There is limited evidence describing the safety and effectiveness of bedaquiline and delamanid containing regimens in children and adolescents with Multidrug-Resistant Tuberculosis (MDR-TB) and Extensively Drug-Resistant Tuberculosis (XDR-TB) globally. In this nationwide descriptive cohort study from Belarus, we examined adverse drug events, time to culture conversion, treatment outcomes including post-treatment recurrence among children and adolescents (<18 years of age) treated with bedaquiline and/or delamanid containing regimens from 2015 to 2019. Of the 40 participants included (55% females; age range 10-17 years), 20 (50%) had XDR-TB and 15 (38%) had resistance to either fluoroquinolone or second-line injectable. Half of the patients received delamanid and another half received bedaquiline with one patient receiving both drugs. AEs were reported in all the patients. A total of 224 AEs were reported, most of which (76%) were mild in nature. Only 10 (5%) AEs were graded severe and one AE was graded life-threatening. A total of 7 AEs (3%) were classified as 'serious' and only one patient required permanent discontinuation of the suspected drug (linezolid). Most of the AEs (94%) were resolved before the end of treatment. All patients culture-positive at baseline (n=34) became culture-negative within three months of treatment. Median time to culture conversion was 1.1 months (interquartile range: 0.9-1.6). Two patients were still receiving treatment at the time of analysis. The remaining 38 patients successfully completed treatment. Among those eligible and assessed at 6 (n=32) and 12 months (n=27) post-treatment, no recurrences were detected. In conclusion, treatment of children and adolescents with MDR-TB and XDR-TB using bedaquiline and/or delamanid containing regimens was effective and had favourable safety profile. Achieving such excellent outcomes under programmatic settings is encouraging for other national tuberculosis programmes, which are in the process of introducing or scaling-up the use of these new drugs in their countries.

Rifampicin-Resistant/Multidrug-Resistant Tuberculosis (RR/MDR-TB) is recognized as a major public health concern globally. In Armenia, the proportion of RR/MDR-TB is increasing among all people affected with TB. We conducted a nationwide cohort study involving analysis of programmatic data to investigate the rates of and factors associated with unfavourable treatment outcomes among patients with RR/MDR-TB registered by the national TB programme from 2014 to 2017 in Armenia. We used Cox regression to identify factors associated with the outcome. Among 451 RR/MDR-TB patients, 80% were men and median age was 46 years. Of them, 53 (11.8%) had Extensively Drug-Resistant Tuberculosis (XDR-TB) and 132 (29.3%) had pre-XDR-TB. Almost half (224, 49.7%) of the patients had unfavourable treatment outcome, which included 26.8% Loss To Follow-Up (LTFU), 13.3% failures and 9.5% deaths. In multivariable analysis, people with pre-XDR-TB [adjusted Hazard Ratio [aHR] 3.13, 95% confidence intervals [CI] 2.16-4.55] and XDR-TB (aHR 4.08, 95% CI 2.45-6.79) had a higher risk of unfavourable outcomes. Patients receiving home-based treatment (71/451, 15.7%) and treatment with new drugs (172/451, 38.1%) had significantly lower risk (aHR 0.45, 95% CI 0.28-0.72 and aHR 0.26, 95% CI 0.18-0.39) of unfavourable treatment outcome.  The proportion of MDR-TB patients reaching favourable treatment outcome in Armenia was substantially lower than the recommended level (75%). The most common treatment outcome was LTFU indicating the need for further assessment of underlying determinants. Home-based treatment looks promising and future studies are required to see if expanding it to all RR/MDR-TB patients is feasible and cost-effective.

To address the sub-optimal treatment outcomes among patients with multidrug-resistant (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB), the National TB Programme in Belarus started using new drugs such as bedaquiline and delamanid in 2015-16. In this study, we assessed cardiovascular safety and effectiveness (culture conversion, treatment outcomes and post-treatment recurrence) of delamanid-containing regimens among adults (>18 years) with MDR-TB or XDR-TB from June 2016 to February 2018. This was a nationwide cohort study involving analysis of routinely collected programme data from the national and six regional TB hospitals. Cardiovascular adverse events (AEs) were classified as serious or not, based on international guidelines. We conducted Cox proportional hazards regression and calculated adjusted hazards ratio(aHR) and 95% confidence intervals(CI) to evaluate factors associated with AEs and unsuccessful treatment outcomes (death, failure and lost-to-follow-up). Of 125 patients enrolled (35, 28% females; mean age 43 years), 85(68%) had XDR-TB. All the patients received delamanid and 20 patients received both delamanid and bedaquiline. Cardiovascular AEs (177 episodes in total), were observed in the majority (73%) of patients but were mild and managed easily. The most common cardiovascular AEs were QTcF prolongation (64/177, 36%) and other electrocardiography (ECG) abnormalities (40/177, 23%). There were two instances of serious AEs leading to death, both of which were not related to delamanid. In multivariable analysis, male sex (aHR 0.72; 95% CI 0.51-0.99), and baseline ECG abnormalities (aHR 1.68; 95% CI 1.19-2.36) were associated with cardiovascular AEs. Median time to culture conversion was 1.1 months (interquartile range: 1.0-2.1). Culture conversion was observed in 115 (92%) patients at six months of treatment and 110 (88%) completed the treatment successfully. Loss to follow-up, failure and death were observed in 6%, 4% and 2% patients respectively. Among those assessed at 12 months post-treatment (n=33), recurrence was seen in one patient. The only factor associated with unsuccessful treatment outcomes in multivariable analysis was baseline Hepatitis C co-infection (aHR 3.61; 95% CI 1.09-11.95). In conclusion, treatment using delamanid-containing regimens was effective and had a favourable safety profile. We hope our findings inform the development of national clinical guidelines and scale-up of new drugs in other countries.

Background: As per national policy, all diagnosed tuberculosis patients in India are to be tested using Xpert® MTB/RIF assay at the district level to diagnose rifampicin resistance. Regardless of the result, samples are transported to the reference laboratories for further testing: first-line Line Probe Assay (FL-LPA) for rifampicin-sensitive samples and second-line LPA(SL-LPA) for rifampicin-resistant samples. Based on the results, samples undergo culture and phenotypic drug susceptibility testing. We assessed among patients diagnosed with tuberculosis at 13 selected Xpert laboratories of Karnataka state, India, i) the proportion whose samples reached the reference laboratories and among them, proportion who completed the diagnostic algorithm ii) factors associated with non-reaching and non-completion and iii) the delays involved., Methods: This was a cohort study involving review of programme records. For each TB patient diagnosed between 1st July and 31st August 2018 at the Xpert laboratory, we tracked the laboratory register at the linked reference laboratory until 30th September (censor date) using Nikshay ID (a unique patient identifier), phone number, name, age and sex., Results: Of 1660 TB patients, 1208(73%) samples reached the reference laboratories and among those reached, 1124(93%) completed the algorithm. Of 1590 rifampicin-sensitive samples, 1170(74%) reached and 1104(94%) completed the algorithm. Of 64 rifampicin-resistant samples, only 35(55%) reached and 17(49%) completed the algorithm. Samples from rifampicin-resistant TB, extra-pulmonary TB and two districts were less likely to reach the reference laboratory. Non-completion was more likely among rifampicin-resistant TB and sputum-negative samples. The median time for conducting and reporting results of Xpert® MTB/RIF was one day, of FL-LPA 5 days and of SL-LPA16 days., Conclusion: These findings are encouraging given the complexity of the algorithm. High non-reaching and non-completion rates in rifampicin-resistant patients is a major concern. Future research should focus on understanding the reasons for the gaps identified using qualitative research methods., Competing Interests: It is declared that none of the authors have any competing interests.