Increase in rifampicin resistance among people previously treated for TB.

People previously treated for TB are at a higher risk of rifampicin-resistant or multidrug-resistant TB (RR/MDR-TB). Uganda's recent RR-TB estimates were not updated, including during the COVID-19 pandemic. Using programmatic data (2012-2021), we report on the distribution and trends in RR-TB among people previously treated for bacteriologically confirmed pulmonary TB (BC-PTB) across six TB clinics in Kampala, Uganda. The RR-TB prevalence between 2012 and 2015 was 0% (95% CI 0-2.3). The prevalence rose significantly in recent years to 7.0% (95% CI 4.4-10.8) between 2016 and 2021 (P < 0.001). RR-TB is increasing among people previously treated for BC-PTB in Kampala; surveillance for RR-TB should be enhanced.

Les personnes précédemment traitées pour TB sont à plus haut risque de TB résistante à la rifampicine ou de TB multirésistante (RR/MDR-TB). Les estimations récentes de l'Ouganda sur la RR-TB n'ont pas été mises à jour, y compris pendant la pandémie de COVID-19. À l'aide de données programmatiques (2012­2021), nous présentons un rapport sur la distribution et les tendances de la RR-TB chez les personnes précédemment traitées pour une TB pulmonaire confirmée bactériologiquement (BC-PTB) dans six cliniques antituberculeuses de Kampala, Ouganda. La prévalence de la RR-TB entre 2012 et 2015 était de 0% (IC 95% 0­2,3). Une augmentation significative de sa prévalence a toutefois été observée au cours des dernières années, atteignant 7,0% (IC 95% 4,4­10,8) entre 2016 et 2021 (P < 0,001). La RR-TB est en augmentation chez les personnes précédemment traitées pour BC-PTB à Kampala ; la surveillance de la RR-TB doit donc être renforcée.

Limited effect of reducing pulmonary tuberculosis incidence amid mandatory facial masking for COVID-19

Tuberculosis (TB) remains a significant health and public issue in many countries. Its incidence and mortality have been decreasing in many countries. The recent COVID-19 could have significant impacts on the transmission and health care for this chronic disease by obligatory facial masking and by affecting healthcare capacities. WHO global tuberculosis in 2021 reported that the TB incidence would rebound at the end of 2020 during COVID-19 pandemic. We wondered if this phenomenon could have existed in Taiwan. We asked whether the trend of TB incidence and mortality would be affected by the COVID-19 epidemic due to their common air transmission route. We also asked whether the incidence of TB in regions with different COVID-19 incidences would be similar. We obtained the yearly new cases of TB and multidrug-resistant TB through Taiwan CDC and estimated the incidence and mortality by the population numbers in 7 administrative regions in Taiwan from 2010 to 2021. The result showed that incidences of TB in recent 10 years show a continuously decreasing trend, even amid the COVID-19 pandemic in 2020-21. Surprisingly, in the low COVID-19 incidence regions of Taiwan, the incidence of TB remained high during the COVID-19 pandemic. We concluded that the decreasing trend of incidence and mortality of TB does not change during the COVID-19 epidemic in Taiwan. The mask-wearing and social distancing could prevent the transmission of COVID-19, however, their effect on the limiting spread of TB may be limited. The health policy decision should take the consideration of the TB rebound, even in the post-COVID-19 era.Copyright © 2023

A historical review of pandemics with a dermatological perspective

We present a literature review of dermatology features in historical pandemics. A pandemic is an epidemic occurring worldwide, or over a very wide area, crossing international boundaries and affecting a large number of people. Smallpox was the first documented pandemic, around 10 000 BC, spread by the inhalation of airborne droplets. A few days after an initial high fever, headache and fatigue, a mucocutaneous maculopapular eruption appeared, which then developed pustules and erosions. The last outbreak occurred in the USA in 1949. Smallpox was eradicated in 1980, following a vaccination programme. Mycobacterium tuberculosis is the causative agent of tuberculosis (TB), an ongoing global pandemic. The earliest documentations were 3300 years ago. In 2020, the World Health Organization (WHO) provisionally estimated 1.5 million deaths globally. Most commonly affecting the lungs, cutaneous TB may present with inflammatory papules, plaques, suppurative nodules and chronic ulcers. Requiring long, complex antibiotic regimens, multidrug resistant TB is an increasing problem. Now extremely rare, yet still with recent outbreaks in 2021 in Madagascar, bubonic plague arrived in Europe in 1346 causing 75-200 million deaths. It is caused by the bacterium Yersinia pestis, transmitted through fleas that have fed on infected rodents. Clinical features include papules, pustules, ulcers and eschars, tender lymphadenopathy and systemic symptoms, and it responds to antibiotics. Syphilis, caused by the bacterium Treponema pallidum, is sexually transmitted. The first known outbreak was during warfare in 1494-5 in Naples, Italy. In 2020, the WHO estimated that, globally, seven million people had new infections. Primary syphilis typically produces a painless, genital ulcer (or chancre). Secondary syphilis presents with a nonitchy, maculopapular erythema over the trunk, palms and soles. Early recognition and antibiotic treatment usually lead to good outcomes. Estimated by the WHO to affect 37.7 million people in 2020, HIV is thought to have mutated from simian immunodeficiency virus by the 1960s in sub-Saharan Africa, spreading to the Caribbean and USA by the late 1960s. Initial symptoms include a fever, headache and lymphadenopathy. Dermatological features are common, including opportunistic cutaneous infections, nonspecific exanthemas, seborrhoeic dermatitis and Kaposi sarcoma. Advances in antiretroviral therapies mean people with HIV can have an excellent prognosis, although the WHO estimated in 2020 that more than 200 000 people with HIV died from concomitant TB. Since 2019, COVID-19 has had a considerable global impact on healthcare. With more than 300 million cases and 5.5 million deaths to date, some services have been overwhelmed owing to large case numbers, variable vaccine uptake, workplace changes to reduce transmission and staff shortages. Cutaneous features include perniosis, urticarial, purpuric, vesicular or maculopapular eruptions. Pandemics throughout history have been repeatedly shown to present with an element of skin involvement. We can utilize this to promote education and early recognition of these features, to facilitate diagnosis and raise awareness of the potential complications of serious diseases.

Trends in pediatric tuberculosis diagnosis utilizing xpert Mycobacterium tuberculosis/Rifampicin in a poor-resource, high-burden region: A retrospective, multicenter study.

Background: The burden of tuberculosis (TB) in Nigeria remains high, and diagnosis in children, a challenge. We aimed to document yield from Xpert Mycobacterium tuberculosis/rifampicin (MTB/RIF) as a mode of diagnosis for children and the variables associated with a positive result. Methods: This was a retrospective review of TB treatment cards of children aged 0-15 years managed from January 2017 to December 2021 across six public tertiary institutions in Nigeria. The data obtained were analyzed using the descriptive and inferential statistics. Statistical significance was set at P < 0.05. Results: Of 1489 children commenced on TB treatment, 1463 (97.9%) had sufficient data for analysis the median age of study participants was 60 months (interquartile range [IQR]: 24, 120), and 814 (55.6%) were males. Xpert MTB/RIF test was performed in 862 (59%) participants and MTB was detected in 171 (19.8%) participants, of which 6.4% (11/171) had RIF resistance reported. The use of Xpert MTB/RIF rose from 56.5% in 2017 to 64% in 2020 but fell to 60.9% in 2021. We found that older age (> 10 years), the presence of pulmonary TB (PTB), and a negative human immunodeficiency virus (HIV) status were associated with positive Xpert MTB/RIF tests (P = 0.002, 0.001, and 0.012, respectively). Conclusion: The utilization of Xpert MTB/RIF in children increased in the years before the COVID-19 pandemic. Factors associated with MTB detection by Xpert MTB/RIF include older age, the presence of PTB, and a negative HIV status. Clinical and radiological evaluation continues to play vital roles in the diagnosis of childhood TB in Nigeria.

Limited effect of reducing pulmonary tuberculosis incidence amid mandatory facial masking for COVID-19.

Although the incidence and mortality rates associated with tuberculosis (TB) have been decreasing in many countries, TB remains a major public health concern. Obligatory facial masking and reduced health-care capacity because of COVID-19 may substantially influence TB transmission and care. The Global Tuberculosis Report 2021 published by the World Health Organization indicated a TB rebound at the end of 2020, which coincided with the COVID-19 pandemic. We explored this rebound phenomenon in Taiwan by investigating whether TB incidence and mortality are affected by COVID-19 because of their common route of transmission. In addition, we investigated whether the incidence of TB varies across regions with different incidences of COVID-19. Data (2010-2021) regarding annual new cases of TB and multidrug-resistant TB were collected from the Taiwan Centers for Disease Control. TB incidence and mortality were assessed in Taiwan's seven administrative regions. Over the last decade, TB incidence decreased continually, even during 2020 and 2021, the years coinciding with the COVID-19 pandemic. Notably, TB incidence remained high in regions with low COVID-19 incidence. However, the overall decreasing trends of TB incidence and mortality remained unchanged during the pandemic. Facial masking and social distancing may prevent COVID-19 transmission but exhibit limited efficacy in reducing TB transmission. Thus, during health-related policymaking, policymakers must consider TB rebound, even in the post-COVID-19 era.

The surfactant inhaled therapy in a complex lung tuberculosis treatment: clinical reviews

The article describes the clinical case reports of patients with respiratory tuberculosis who were hospitalized at the Regional Clinical Antituberculosis Center in Kursk. One of them was in the pediatric department for patients with tuberculosis of respiratory organs and the other in the 1st department for patients with multidrug-resistant tuberculosis. As pathogenetic therapy in the complex treatment of pulmonary tuberculosis, in the intensive phase of anti-tuberculosis chemotherapy, we added inhalation therapy with surfactant (medicinal product surfactant-BL lyophilisate for emulsion preparation, 75 mg, manufactured by Biosurf LLC, Russia) according to the instructions to the drug. Treatment of pulmonary tuberculosis is performed by multiple inhalations of surfactant-BL as part of complex therapy against the background of fully deployed antituberculosis drugs (ATD), i.e. when the patient empirically or based on data on drug sensitivity of the pathogen is selected 4-6 ATD that are well tolerated by the patient in the prescribed dose and combination. It should be noted that an adult patient during the intensive phase of anti-tuberculosis chemotherapy had COVID-19. Against the background of inhalation therapy with surfactant, it was possible to stabilize the clinical and radiological condition of the patients, and to improve their condition. Clinically it was expressed in reduction of coughing, increase of tolerance to physical exertion. For example, according to spirometry data on the admission of an adult patient and in dynamics, the vital capacity index (VCI) increased from an extremely sharp decrease (31.25%) to 75%, which corresponded to a very mild decrease. At the moment the patient from the children's ward is completing a course of antituberculosis therapy with small residual changes in the lungs, and the adult patient was operated on at the Russian Ministry of Health at the Federal State Budgetary Institution "National Research Center of Pulmonary Medicine” for installation of a bronchial valve. Based on the above, we can conclude about the successful, pathogenetically sound use of surfactant-BL in patients with respiratory tuberculosis in both children and adults. © 2022, Remedium Group Ltd. All rights reserved.

The surfactant inhaled therapy in a complex lung tuberculosis treatment: clinical reviews

The article describes the clinical case reports of patients with respiratory tuberculosis who were hospitalized at the Regional Clinical Antituberculosis Center in Kursk. One of them was in the pediatric department for patients with tuberculosis of respiratory organs and the other in the 1st department for patients with multidrug-resistant tuberculosis. As pathogenetic therapy in the complex treatment of pulmonary tuberculosis, in the intensive phase of anti-tuberculosis chemotherapy, we added inhalation therapy with surfactant (medicinal product surfactant-BL lyophilisate for emulsion preparation, 75 mg, manufactured by Biosurf LLC, Russia) according to the instructions to the drug. Treatment of pulmonary tuberculosis is performed by multiple inhalations of surfactant-BL as part of complex therapy against the background of fully deployed antituberculosis drugs (ATD), i.e. when the patient empirically or based on data on drug sensitivity of the pathogen is selected 4-6 ATD that are well tolerated by the patient in the prescribed dose and combination. It should be noted that an adult patient during the intensive phase of anti-tuberculosis chemotherapy had COVID-19. Against the background of inhalation therapy with surfactant, it was possible to stabilize the clinical and radiological condition of the patients, and to improve their condition. Clinically it was expressed in reduction of coughing, increase of tolerance to physical exertion. For example, according to spirometry data on the admission of an adult patient and in dynamics, the vital capacity index (VCI) increased from an extremely sharp decrease (31.25%) to 75%, which corresponded to a very mild decrease. At the moment the patient from the children's ward is completing a course of antituberculosis therapy with small residual changes in the lungs, and the adult patient was operated on at the Russian Ministry of Health at the Federal State Budgetary Institution "National Research Center of Pulmonary Medicine” for installation of a bronchial valve. Based on the above, we can conclude about the successful, pathogenetically sound use of surfactant-BL in patients with respiratory tuberculosis in both children and adults. © 2022, Remedium Group Ltd. All rights reserved.

Structures of mycobacterial ATP synthase bound to inhibitors

Tuberculosis is the second leading cause of death by infectious disease worldwide after COVID-19. Mycobacterium tuberculosis, which causes tuberculosis, is showing alarming levels of resistance to first-line antibiotics, jeopardizing efforts to eradicate the disease. Research is underway to develop new, safer drugs to treat drug resistant tuberculosis. One of these breakthrough drugs is bedaquiline, which targets the mycobacterial ATP synthase, an essential enzyme in mycobacteria. The success of bedaquiline, which has become a cornerstone of treatment for multidrug-resistant and extensively drug-resistant tuberculosis, demonstrates the importance of the mycobacterial ATP synthase as a key drug target against M. tuberculosis. Since the discovery of bedaquiline in 2005, there has been a renewed interest in developing new and improved mycobacterial ATP synthase inhibitors. We have determined electron cryomicroscopy structures of M. smegmatis ATP synthase in complex with inhibitors. We provide detailed mechanistic and structural insights into the mode of action of these compounds, which will support medicinal chemistry efforts to design new tuberculosis drugs. Our work reveals new inhibitor binding sites in the enzyme, opening the route for development of new classes of compounds and improved inhibitors. Copyright © 2022

Multidrug-resistant Tuberculosis and COVID-19 Coinfection with Diabetes Mellitus in Medan, Indonesia: A Case Report

BACKGROUND: Coronavirus disease 2019 (COVID-19) has distracted the global health system due to significant morbidity and mortality. There are increasing mortality rates related to the existence of comorbidities. Due to immunologic conditions, other infectious diseases, such as multidrug-resistant tuberculosis (MDR-TB), might coinfect with COVID-19. We describe a case of MDR-TB with diabetes mellitus and critical COVID-19 patient with fatal outcome. CASE REPORT: A 60-year-old man was admitted to our hospital with shortness of breath for 2 days. A history of recurrent shortness of breath has had developed for about 7 months. Room air oxygen saturation was at 66%. RT-PCR SARS-CoV-2 nasopharynx swab result was positive. The chest X-ray series result showed destroyed left lung with increasing infiltrate in the lower right lung. The patient was diagnosed with pulmonary MDR-TB based on GeneXpert and LPA (Line Probe Assay) test 6 months prior and also has had history of diabetes mellitus for 7 years. Then, the patient was diagnosed with COVID-19, pulmonary MDR-TB, and diabetes mellitus. MDR-TB regimen, anti-diabetic medication, and management of COVID-19 were carried out. On the 6th day, the patient’s condition worsened to the point, where he needed intubation. The patient eventually passed away. CONCLUSION: The treatment outcome was highly related to the severity of COVID-19 symptoms and complications of comorbidities when patients are admitted to the hospital. The early screening and treatment of COVID-19 are important to prevent deteriorating clinical conditions caused by comorbidities.

TB-PRACTECAL: study protocol for a randomised, controlled, open-label, phase II-III trial to evaluate the safety and efficacy of regimens containing bedaquiline and pretomanid for the treatment of adult patients with pulmonary multidrug-resistant tuberculosis.

BACKGROUND: Globally rifampicin-resistant tuberculosis disease affects around 460,000 people each year. Currently recommended regimens are 9-24 months duration, have poor efficacy and carry significant toxicity. A shorter, less toxic and more efficacious regimen would improve outcomes for people with rifampicin-resistant tuberculosis. METHODS: TB-PRACTECAL is an open-label, randomised, controlled, phase II/III non-inferiority trial evaluating the safety and efficacy of 24-week regimens containing bedaquiline and pretomanid to treat rifampicin-resistant tuberculosis. Conducted in Uzbekistan, South Africa and Belarus, patients aged 15 and above with rifampicin-resistant pulmonary tuberculosis and requiring a new course of therapy were eligible for inclusion irrespective of HIV status. In the first stage, equivalent to a phase IIB trial, patients were randomly assigned one of four regimens, stratified by site. Investigational regimens include oral bedaquiline, pretomanid and linezolid. Additionally, two of the regimens also included moxifloxacin (arm 1) and clofazimine (arm 2) respectively. Treatment was administered under direct observation for 24 weeks in investigational arms and 36 to 96 weeks in the standard of care arm. The second stage of the study was equivalent to a phase III trial, investigating the safety and efficacy of the most promising regimen/s. The primary outcome was the percentage of unfavourable outcomes at 72 weeks post-randomisation. This was a composite of early treatment discontinuation, treatment failure, recurrence, lost-to-follow-up and death. The study is being conducted in accordance with ICH-GCP and full ethical approval was obtained from Médecins sans Frontières ethical review board, London School of Hygiene and Tropical Medicine ethical review board as well as ERBs and regulatory authorities at each site. DISCUSSION: TB-PRACTECAL is an ambitious trial using adaptive design to accelerate regimen assessment and bring novel treatments that are effective and safe to patients quicker. The trial took a patient-centred approach, adapting to best practice guidelines throughout recruitment. The implementation faced significant challenges from the COVID-19 pandemic. The trial was terminated early for efficacy on the advice of the DSMB and will report on data collected up to the end of recruitment and, additionally, the planned final analysis at 72 weeks after the end of recruitment. TRIAL REGISTRATION: Clinicaltrials.gov NCT02589782. Registered on 28 October 2015.

Study of efficacy, safety and outcomes of shorter course regimen at nodal DRTB Centre SNMC Agra

Background: Tuberculosis (TB) is a communicable disease that is a major cause of illness and one of the leading causes of death. Until the COVID-19 pandemic, TB was the leading cause of death from a single infectious agent, ranking above HIV. Multi drug-resistant TB remains a public health crisis. In this situation, an attempt of using the shorter course Regimen to face the MDR-TB crisis as an alternate method proves to be promising. Therapy of MDR-TB using shorter course regimen is crucial and essential to explore, as it has the potential to increase the success of MDR-TB treatment. Methods: The proposed study was a hospital based, nonrandomized and without control group observational and prospective study, in cohort of 180 DRTB patients conducted at Nodal DRTB Centre, SNMC AGRA. Results: Among 180 patients 54% were male and 46% female. Maximum number of patients 39% in 21-30 years of age group.48% patients were known to their contacts.54% patients developed resistance due to failure of previous regimen.126 patients were reported with adverse effects. Cough was the most common clinical feature.46 completed the treatment.39% patients were declared cured. Conclusion: 70% of the patients faced adverse events during the course. 1.6% patients required change in regimen.61% completed the treatment and 39% were declared cured.

Pediatric Dr. TB: A neglected epidemic

Background: Amidst fight against COVID-19 pandemic, efforts to mitigate other communicable disease threatening public health including TB has taken a back step. Limited evidence exists about the change in prevalence of Pediatric Dr. TB post 2020. Objective: The study aimed to find out the change in prevalence of Pediatric DR TB pre and post 2020. Methods: Descriptive retrospective and prospective study. Pediatric Dr. TB was defined on the basis of Gene X pert/ line probe assay and/ or drug susceptibility testing (DST). Results: Prevalence of Pediatric Dr. TB in year 2018, 2019, 2020 and 2021 (January-September) were 17.4%, 15.1%, 18.4% and 16.6% respectively in the age group of 1-18 years. Majority (93.9%, 90.5%, 89.5%, 96.8%) had pulmonary TB. Cumulative prevalence of Pediatric Dr. TB for the 24 months of year 2018 & 2019 was 16.3% while it was 17.6% for the 21 months of year 2020 & 2021 (January-September). It reveals an increase of 4.1%. On extrapolating the prevalence rate of Dr. TB for the 9 months of year 2021, prevalence rate of Dr. TB by the end of year 2021 is expected to be 22.1%. Among Dr. TB, prevalence (%) of XDR TB;MDR TB;monoresistant TB for year 2018, 2019, 2020 & 2021 was (10.9,88.0,1.1), (5.1,92.8,2.1), (3.4,94.9,1.7) and (7.4,91.6,1.0) respectively. Conclusion: With this report of increase in prevalence of Pediatric Dr. TB, it has become the need of the hour to start focusing on TB vigorously and to take uncompromising relentless measures to achieve the country's vision to eliminate TB by 2025.

Beware of TB amid COVID 19 pandemic

Background: Tubercolosis has a worrisome connection with novel corona virus.Lingering respiratory symptoms in people who have recovered from Covid could well be mistaken as residual issues of Covid or secondary bacterial infections, missing TB diagnosis totally. Methods: A 28 year old female doctor by profession, initially asymptomatic tested Covid -19 positive as a part of contact tracing. On the 15th day, she developed fever, dry cough and fatigue which persisted even after taking symptomatic treatment. Repeat Covid testing was negative.HRCT chest was normal.Sputum CBNAAT was negative and other relevant blood investigations were normal. On examination she was febrile and matted subcentimetric right cervical lyphnodes(LN) were palpable.Excision Biopsy of cervical LN was done and report suggested Kikuchi's disease.As a part of work up of Pyrexia of Unknown Origin, she undertwent 18-FDG PET whole body CT scan and showed mediastinal lymph node uptake(2R,4R LN station). Mediastinoscopic biopsy report showed tuberculosis and Gene Expert showed mycobacterium complex with Rifampicin resistance. Results: Based on clinical, radiological and laboratory findings, MDR LN tuberculosis was diagnosed.Patient wad started on MDR TB regimen and symptoms got improved. Conclusion: There is an increased likelihood of tuberculosis in post COVID patients due to many factors like lung inflammation, altered immunity and stress due to COVID, use of steroids and uncontrolled diabetes.Therefore active tuberculosis should be vigorously ruled out in any post covid patients with continuous fever.

Comparison of Disability-Adjusted Life Years (DALYs) and Economic Burden on People With Drug-Susceptible Tuberculosis and Multidrug-Resistant Tuberculosis in Korea.

In the future, tuberculosis (TB) will place a heavy burden on the aging population in Korea. To prepare for this crisis, it is important to analyze the disease burden trend of drug-susceptible tuberculosis (DS-TB) and multidrug-resistant tuberculosis (MDR-TB). Measuring disability-adjusted life years (DALYs) and economic burden on MDR-TB patients can help reduce the incidence of TB. Accordingly, in this study, we measured the DALYs and economic burden on DS-TB and MDR-TB patients in 2014-2017 using a combination of National Health Insurance claims data, Annual Report on the Notified TB data, and Statistics Korea's mortality data. The incidence-based DALY approach implemented involved the summation of years of life lost and years lived with disability. For measuring economic burden, direct and indirect costs incurred by patients were totaled. From 2014 to 2017, DALYs per 100,000 people with DS-TB were 56, 49, 46, and 40, respectively, and DALYs per 100,000 people with MDR-TB were 3, 2, 2, and 2, respectively. The economic burden for the DS-TB population from 2014 to 2017 was $143.89 million, $136.36 million, $122.85 million, and $116.62 million, respectively, while that for MDR-TB was $413.44 million, $380.25 million, $376.46 million and $408.14 million, respectively. The results showed a decreasing trend in DALYs and economic burden for DS-TB, whereas MDR-TB was still found to be burdensome without a specific trend. With respect to age, the economic burden for both DS-TB and MDR-TB was higher among men than among women till ≤ 79 years. Conversely, the economic burden for women aged ≥80 years was higher as compared to their male counterparts. In conclusion, the incidence and spread of TB in all areas of society must be suppressed through intensive management of MDR-TB in the older population. We hope that the national TB management project will proceed efficiently when the infectious disease management system is biased to one side due to the COVID-19 pandemic.

Impact of COVID-19 lockdown on mental health of patients with multi-drug resistant tuberculosis (MDRTB) in tertiary care centre Mumbai

Background &Objective : Multi-Drug Resistant Tuberculosis (MDRTB) and depression act synergistically that magnify the burden of disease. The present study aims to understand the differences in depression scale using Patient Health Questionnaire-9 (PHQ-9) over the time during the COVID-19 pandemic which may cause mental and psychological changes in the patients with MDRTB. Method: A total of 155 treatment naive adults and adolescents MDRTB are enrolled in an ongoing cohort. Each participant completes PHQ-9 to assess depression at baseline, 2 weeks, 1, 2, 3, 4, 5, 6, 12, 18, 24 months of treatment and post treatment 6 and 12 months. Differences in the PHQ9 scores for visits before COVID-19, during 1st lockdown, in unlock phase and 2nd lockdown were assessed by Chi-squared test and t-test and p<0.05 were considered statistically significant. Results: Out of 155 participants with median age of 27 years' 102 (65.8%) were females A significant difference was seen in the overall PHQ-9 scores across each time period (p<0.001). Also, significant changes were seen in overall PHQ-9 scores before COVID-19 and 1st lockdown (p<0.001), during unlock phase, 2nd lockdown (p<0.001) and without lockdown and during 1st and 2nd lockdowns (p<0.001). During 1st lockdown and unlock phase (p=0.165), there were no significant differences seen in the PHQ-9 scores. Conclusion: In this ongoing study, changes in the overall depression scale were significantly associated with COVID-19 lockdown, during unlock phase and 2nd lockdown phase. PHQ-9 screening can be useful for patients who may benefit from additional support and counselling during the treatment during COVID-19 pandemic.

Tuberculosis

Tuberculosis (TB) is a communicable, airborne infectious disease caused by the bacterium Mycobacterium tuberculosis (MTB). A quarter of the world's population is infected with TB, affecting all age groups. Infection with MTB results in latent or active disease. Latent infection is associated with a 10% lifetime risk of developing active disease, but this is much higher in those with concurrent immunosuppression. Despite being both preventable and curable, TB remains the leading cause of global death from a single infectious agent. Active disease most commonly affects the lungs but can spread to cause extrapulmonary disease anywhere in the body. Over half of individuals in the UK now present with features of extrapulmonary TB, those with HIV being at particular risk. In all cases, obtaining samples for TB culture is absolutely vital. Standard treatment is with quadruple therapy for 6 months, extended in TB meningitis and often TB bone infection. Adjunctive corticosteroids have proven benefit in TB meningitis and TB pericarditis, and can be considered in other circumstances, such as paradoxical reactions to starting treatment in miliary TB. Despite recent gains in diagnosing and treating TB cases worldwide, the global COVID-19 pandemic is likely to have significantly affected recent progress.

AEROSOLIZATION OF RECOMBINANT INTERFERON GAMMA USING I-NEB-MINI JET NEBULIZER

TYPE: TOPIC: Pharmacotherapeutics PURPOSE: The i-NEB-MiniTM is a jet nebulizer designed for controlled delivery of small (< 2 mL) volumes of potent drugs to the deep lung. The purpose of this study was to determine aerosol parameters and post nebulization drug activity of a novel formulation of recombinant Interferon Gamma (rIFNγ), a pluripotent molecule with Th1 helper cell activity. METHODS: rINFγ (200 μg/mL) was aerosolized using i-NEB-MiniTM driven by a portable compressor at 3.5 L/min. Two (2) mL was aerosolized into a Next Generation Impactor (NGI) using a 15 L/min vacuum. Aerosol parameters (MMAD, GSD, Total Respirable Dose) were determined using an HPLC assay (Vectura Ltd., UK). Bioactivity pre-/post-nebulization was determined using an HLADR assay (PBL Assay Sciences, Piscataway, NJ, USA). RESULTS: The MMAD, GSD and Total Respirable dose from a 200 μg/mL formulation (n=6) was 2.5 (± 0.2), 1.6 (± 0.4) and 123.7 (± 19.8) μg respectively. The bioactivity pre- and post-nebulization was consistent with the EP standard suggesting that nebulization did not affect biological activity of the protein. CONCLUSIONS: This study indicates that a clinically relevant and reproducible dose of rINFγ can be delivered with i-NEB-MiniTM. Bioactivity assay indicates that aerosol rINFγ retains protein integrity after nebulization. CLINICAL IMPLICATIONS: rINFγ is an immunomodulatory pleiotropic cytokine with potential for treatment of respiratory diseases such as Pulmonary Fibrosis, MDRTB, COPD and SARS-CoV-2. The results indicate that a clinically relevant dose of rINFγ can be aerosolized using the i-NEB-MiniTM jet nebulizer. DISCLOSURE: Stony Brook and New York University hold patents on the use of inhaled interferon licensed to InspiRx, Inc. Dr. Smaldone consults to InspiRx and is a member of the advisory board. Mr. Shukla and Dr. Toddywala are employees of InspiRx. KEYWORD: immunomodulation

Causes of multidrug-resistant tuberculosis from the perspectives of health providers: challenges and strategies for adherence to treatment during the COVID-19 pandemic in Brazil.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is a serious phenomenon on a global scale that can worsen with the COVID-19 pandemic. The study aimed to understand the perceptions of health professionals about MDR-TB, their strategies to ensure adherence to treatment and their challenges in the context of the COVID-19 pandemic in a priority municipality for disease control. METHODS: We conducted a qualitative study and recruited 14 health providers (four doctors, three nurses, three nursing technicians, three nursing assistants and a social worker) working in a city in the state of São Paulo, Brazil. Remote semi-structured interviews were conducted with the participants. For data analysis, the thematic content analysis technique was applied according to the study's theoretical framework. RESULTS: The study revealed the causes of MDR-TB are associated with poverty, vulnerability, and social risk. A pre-judgement from the providers was observed, namely, all patients do not adhere due their resistance and association with drug abuse or alcoholism. The study also observed difficulty among health providers in helping patients reconstruct and reframe their life projects under a care perspective, which would strengthen adherence. Other issues that weakened adherence were the cuts in social protection and the benefits really necessary to the patients and a challenge for the providers manage that. The participants revealed that their actions were impacted by the pandemic and insecurity and fear manifested by patients after acquiring COVID-19. For alleviating this, medical appointments by telephone, delivery of medicine in the homes of patients and visits by health professionals once per week were provided. CONCLUSION: The study advances knowledge by highlighting the challenges faced by the health system with the adherence of patients with MDR-TB in a context aggravated by the pandemic. An improvement in DOT is really necessary to help the patients reframe their lives without prejudices, face their fears and insecurity, recover their self-esteem and motivate in concluding their treatment.

Survey data of multidrug-resistant tuberculosis, Tuberculosis patients characteristics and stress resilience during COVID-19 pandemic in West Sumatera Province, Indonesia.

This set of data presents a survey data describing multidrug-resistant tuberculosis, tuberculosis patients characteristics and stress resilience during COVID-19 pandemic in West Sumatera Province, Indonesia. The data were gathered from multidrug-resistant tuberculosis, tuberculosis patients through a survey distributed by an online questionnaire, assesing patients characteristics (age, sex, level of education, working status, history of close contact to patients with multidrug resistant tuberculosis and tuberculosis, smoking, alcohol consumption, cavitary pulmonary, diabetes mellitus, nutritional status and tuberculosis outside the lung) and stress resilience (3 items), from 15th July until 7th August 2020. The samples were collected 73 multidrug resistant tuberculosis patients and 219 tuberculosis patients in West Sumatera Province, Indonesia who were willing to fill an online questionnaire. SPSS version 23.0 was used to analyzed the data by descriptive and inferential statistics. The data will help to identify mental health problems and potentially as a warning sign that can support for health education interventions among multidrug-resistant tuberculosis and tuberculosis patients during COVID-19 pandemic.