The 10-year health impact, economic impact, and return on investment of the South African molecular diagnostics programme for HIV, Tuberculosis and SARS-CoV-2 (preprint)

To ensure there is adequate investment into diagnostics, an understanding of the magnitude of impact and return on investment is necessary. We therefore sought to understand the health and economic impacts of the molecular diagnostic programme in South Africa, to deepen the under-standing on the broad value of diagnostics and guide future healthcare investments. We calcu-lated the 10-year (where data were available) total cost and DALYs averted associated with molecular diagnosis of molecular TB testing (2013-2022), HIV viral load monitoring (2013-2022), early infant diagnosis of HIV infection (2013-2022), and SARS-CoV-2 testing (2020-2022). We then calculated the economic value associated with those health gains and subsequent return on investment. Since the inception of the molecular diagnostics programme in South Africa, 3,035,782 DALYs have been averted as a direct consequence of this pro-gramme. This has generated an estimated $20.5 billion in economic value due to these health gains. The return on investment varied by specific diagnostic test (19.0 for tuberculosis, 1.4 for HIV viral load testing, 64.8 for early infant diagnosis of HIV, and 2.5 for SARS-CoV-2), for an average of 9.9 for the entire molecular diagnostics programme between 2013 and 2022- or $9.9 of value for each $1 invested. The molecular diagnostics programme in South Africa gen-erated a significant amount of health gains and economic value associated with these health gains, and the return-on-investment rivals other high-impact public health interventions such as childhood vaccination. Consequently, the molecular diagnostics programme in South Africa is highly impactful, and will continue to be an excellent investment of South African public health expenditure.

The Global Impact of COVID-19 on Tuberculosis: A Thematic Scoping Review, 2020-2023 (preprint)

Background: This thematic scoping review of publications sought to understand the global impact of COVID-19 on tuberculosis (TB), interpret the scope of resonating themes, and offer policy recommendations to stimulate TB recovery and future pandemic preparedness. Data Sources: Publications were captured from three search engines, PubMed, EBSCO, and Google Scholar, and applicable websites written in English from January 1, 2020, to April 30, 2023. Study Selection: Our scoping review was limited to publications detailing the impact of COVID-19 on TB. Original research, reviews, letters, and editorials describing the deleterious and harmful––yet sometimes positive–– impact of COVID-19 (sole exposure) on TB (sole outcome) were included. The objective was to methodically categorize the impacts into themes through a comprehensive review of selected studies to provide significant health policy guidance. Data Extraction: Two authors independently screened citations and full texts, while the third arbitrated when consensus was not met. All three performed data extraction. Data Synthesis/Results: Of 1,755 screened publications, 176 (10%) covering 39 countries over 41 months met the inclusion criteria. Ten principal themes were established, which encompassed TB’s care cascade, patient-centered care, psychosocial issues, and health services: 1) case-finding and notification (n=45; 26%); 2) diagnosis and laboratory systems (n=19; 10.7%) 3) prevention, treatment, and care (n=22; 12.2%); 4) telemedicine/telehealth (n=12; 6.8%); 5) social determinants of health (n=14; 8%); 6) airborne infection prevention and control (n=8; 4.6%); 7) health system strengthening (n=22; 13%); 8) mental health (n=13; 7.4%); 9) stigma (n=11; 6.3%); and 10) health education (n=10; 5.7%). Limitations: Heterogeneity of publications within themes. Conclusions: We identified ten globally generalizable themes of COVID-19’s impact on TB. These thematic areas will guide evidence-informed policies to strengthen comprehensive global responses, recovery for TB, and future airborne pandemic preparedness.

Interaction between type 2 diabetes and past COVID-19 on active tuberculosis (preprint)

BACKGROUND The global setback in tuberculosis (TB) prevalence and mortality in the post-COVID-19 era have been partially attributed to pandemic-related disruptions in healthcare systems. The additional biological contribution of COVID-19 to TB is less clear. The goal of this study was to determine if there is an association between COVID-19 in the past 18 months and a new TB episode, and the role played by type 2 diabetes mellitus (DM) comorbidity in this relationship.METHODS A cross-sectional study was conducted among 112 new active TB patients and 373 non-TB controls, identified between June 2020 and November 2021 in communities along the Mexican border with Texas. Past COVID-19 was based on self-report or positive serology. Bivariable/multivariable analysis were used to evaluate the odds of new TB in hosts with past COVID-19 and/or DM status.RESULTS The odds of new TB were higher among past COVID-19 cases vs. controls, but only significant among DM patients (aOR 2.3). The odds of TB given DM was 2.7-fold among participants without past COVID-19 and increased to 7.9-fold among those with past COVID-19.CONCLUSION DM interacts with past COVID-19 synergistically to magnify the risk of TB. Latent TB screening and prophylactic treatment, if positive, is recommended in this COVID-19/DM/latent TB high-risk group.

Private sector tuberculosis care quality during the COVID-19 pandemic: A repeated cross-sectional standardized patients study of adherence to national TB guidelines in urban Nigeria (preprint)

Only a third of TB cases in Nigeria in 2020 were diagnosed and notified, in part due to low detection and underreporting from the private health sector. Using a standardized patient (SP) survey approach, we assessed how management of presumptive TB in the private sector aligns with national guidelines and whether this differed from a study conducted before the start of the COVID-19 pandemic. Thirteen standardized patients presented a presumptive TB case to 511 private providers in urban areas of Lagos and Kano states in May and June 2021. Private provider case management was compared with national guidelines divided into three main steps: SP questioned about cough duration; sputum collection attempted for TB testing; and non-prescription of anti-TB medications, antibiotics, and steroids. SP visits conducted in May-June 2021 were directly compared to SP visits conducted in the same areas in June-July 2019. Overall, only 145 of 511 (28%, 95% CI: 24.5-32.5%) interactions were correctly managed according to Nigerian guidelines, as few providers completed all three necessary steps. Providers in 71% of visits asked about cough duration (362 of 511, 95% CI: 66.7-74.7%), 35% tested or recommended a sputum test (181 of 511, 95% CI: 31.3-39.8%), and 79% avoided prescribing or dispensing unnecessary medications (406 of 511, 95% CI: 75.6-82.8%). COVID-19 related questions were asked in only 2.4% (12 of 511, 95% CI: 1.3-4.2%) of visits. During the COVID-19 pandemic, few providers completed all steps of the national guidelines. Providers performed better on individual steps, particularly asking about symptoms and avoiding prescription of harmful medications. Comparing visits conducted before and during the COVID-19 pandemic showed that COVID-19 did not significantly change the quality of TB care. Key MessagesO_ST_ABSWhat is already known on this topicC_ST_ABSO_LILess than half of new TB cases in Nigeria are diagnosed and notified. As most initial health care seeking for TB in Nigeria occurs in the private sector, increasing the quality of TB care in the private sector is of great importance. C_LIO_LICOVID-19 may have put further stressors on TB care quality due to changes in care seeking behavior, stigma against COVID-19, and disproportionate attention at the health system level on pandemic control. C_LIO_LIThis study explored whether private providers practices are in alignment with national standards for TB screening in Nigeria, how these practices have changed following the onset of the COVID-19 pandemic, and what factors are associated with providers that deliver clinically correct TB screening services. C_LI What this study addsO_LIFewer than one-third of the SP visits conducted in this study were correctly managed according to the Nigerian National TB and Leprosy Control Program guidelines. C_LIO_LIClinical correctness of TB care in the private sector of urban Nigeria has not been majorly affected by COVID-19 according to our study results. C_LIO_LIOur results indicate that very little observed attention was paid to COVID-19 in this sample of private facilities. C_LI How this study might affect research, practice or policyO_LIIncreased efforts to engage and support private providers, and implementing solutions such as working with drug shop proprietors to make referring for testing a standard part of their practice may help reduce the testing bottleneck at drug shops. C_LIO_LIAlthough Nigeria has maintained pre-pandemic levels of TB notification, it is important to establish high-quality screening by all providers to find the missing patients with TB and close the gap in TB notification. C_LI

A novel multi class disease detection of chest x-ray images using deep learning with pre trained transfer learning models for medical imaging applications (preprint)

Images from chest X-rays (CXR) are thought to help observe and research various kinds of pulmonary illnesses. Several works were suggested in the literature for recognizing unique lung diseases, and only a few studies were focused on developing a model to identify joint classes of lung diseases. A patient with a negative diagnosis for one condition may have the other disease, and vice versa. However, since many illnesses are lung-related, a patient can have multiple illnesses simultaneously. This paper proposes a deep learning (DL)-based pre-trained transfer learning (TL) model for effectively detecting and classifying the multiclass diseases of lung CXR images. The system involves five phases: preprocessing, dataset balancing, feature learning, feature selection, and multiclass classification. Firstly, the CXR images are preprocessed by performing filtering, contrast enhancement, and data augmentation. After that, the dataset balancing is performed using the Synthetic Minority Oversampling Technique (SMOTE). Next, the features are learned using a spatial and channel-attention-based Xception Network (SCAXN). The optimal features are selected using nonlinear decreasing inertia weight-based rock hyraxes swarm optimization (NIWRHSO). Finally, the multiclass classification uses a soft sign-incorporated bidirectional gated recurrent unit (SBIGRU). Two public datasets, COVID-19 Radiography (C19RY) and Tuberculosis CXR (TB-CXR), have been obtained from Kaggle, and the outcomes confirmed that the proposed system attains superior results to prevailing methods.

Ocean & seas: Novel biomedical resources for anti-infection of SARS-CoV-2 (preprint)

This article briefly reviews ocean and seas as huge and novel biomedical resources for anti-infection, which includes tuberculosis, H. Pylori, and HIV infection as well as SARS-CoV-2, and as promising biomedical resources for infection-induced major non-communicable diseases (mNCDs), such as cardiovascular disease, diabetes, and cancer. These marine natural products (MNPs) and organisms include sea cucumbers, sea snake, sponge, marine algae and microalgae, etc. As key biomedical resources for the discovery of marine drugs, bioactive molecules, and agents for treatment of infectious diseases and mNCDs, MNPs have bioactive potentials of antioxidant, anti-infection, anti-inflammatory, anticoagulant, anti-diabetic effects, and cancer treatment. In addition, their anti-inflammatory mechanisms for infectious diseases are also involved. It’s time to protect ocean ecosystem for human better sustainable development in the new era of ocean economy.

Marine natural products and human immunity: Novel biomedical resources for anti-infection of SARS-CoV-2 and related cardiovascular disease (preprint)

Major marine natural products (MNPs) and marine organisms include sea urchin, sea squirts or ascidians, sea cucumbers, sea snake, sponge, soft coral, marine algae, and microalgae. As vital biomedical resources for the discovery of marine drugs, bioactive molecules, and agents for treatment of infectious diseases and major non-communicable diseases (mNCDs), these MNPs have bioactive potentials of antioxidant, anti-infection, anti-inflammatory, anticoagulant, anti-diabetic effects, cancer treatment, and improvement of human immunity. This article reviews MNPs as huge and novel biomedical resources for anti-infection of coronavirus (SARS-CoV-2 and its variants), as well tuberculosis, H. Pylori, and HIV infection, and as promising biomedical resources for SARS-CoV-2 infection related cardiovascular disease (irCVD), and other mNCDs, such as diabetes and cancer. In addition, the anti-inflammatory mechanisms of current MNPs against SARS-CoV-2 infection which link to human immunity are also involved. It’s time to protect this ecosystem for human better sustainable development in the new era of ocean economy.

Association Between Presence of Bacillus Calmette-Guerin Vaccine Scar and Coronavirus Disease 2019 (preprint)

Objective: Bacillus Calmette-Guerin (BCG) vaccine is administered for protection against tuberculosis and may also have beneficial effects against some viral respiratory tract infections. The low incidence and mortality of coronavirus disease (COVID-19) in countries that have BCG vaccination program is impressive, and some studies have shared contradictory results. In this study, it was aimed to investigate the relationship between BCG vaccination which is confirmed by BCG scar, and the frequency and course of COVID-19. Methods: : Among 490 patients who applied to the outpatient clinic for Pulmonary and Enfectious Diseases between March 2021 and June 2021, 400 patients who accepted to participate in the study were included. After the consent of patients; age, gender, body mass index, comorbidities, smoking, history and the progress of COVID-19 of these patients were investigated; presence and number of BCG scar were recorded by physician. Data from groups with and without COVID-19 history were compared. Results: : Of the 400 patients 228 (57%) were female. Mean age was 39.65 ± 13.53. 188 (47%) patients had a history of COVID-19. There was no relation between presence and number of the BCG scar and COVID-19 related hospitalization and intensive care unit admission. When groups with and without COVID-19 history compared, no statistically significant difference was found with the presence and number of BCG scars (p>0,05). Conclusion: No association was found between the presence or number of BCG scars and the frequency and course of COVID-19 in individuals with BCG vaccination history confirmed by the presence of BCG vaccine scars.

Changes in the medical admissions and mortality amongst children in four South African hospitals following the COVID -19 pandemic: A five-year review. (preprint)

BackgroundVulnerable children from poor communities with high HIV and Tuberculosis(TB) burdens were impacted by COVID-19 lockdowns. Concern was raised about the extent of this impact and anticipated post-pandemic surges in mortality. MethodsInterrupted time series segmented regression analyses were done using routinely collected facility-level data of children admitted for medical conditions at four South African referral hospitals. Monthly admission and mortality data over a 60-month period from 01 April 2018 to 31 January 2023 was analysed using models which included dummy lockdown level variables, a dummy post-COVID period variable, Fourier terms to account for seasonality, and excess mortality as a proxy for healthcare burden. ResultsOf the 45 015 admissions analysed, 1237(2{middle dot}75%) demised with significant decreases in admissions during all the lockdown levels, with the most significant mean monthly decrease of 450(95%, CI=657{middle dot}3, -244{middle dot}3) p<0{middle dot}001 in level 5 (the most severe) lockdown. There was evidence of loss of seasonality on a six-month scale during the COVID periods for all admissions (p=0{middle dot}002), including under-one-year-olds (p=0{middle dot}034) and under-five-year-olds (p=0{middle dot}004). No decreases in mortality accompanied decreased admissions. Post-pandemic surges in admissions or mortality were not identified in children with acute gastroenteritis, acute pneumonia and severe acute malnutrition. ConclusionDuring the COVID-19 pandemic, paediatric admissions in 4 hospitals serving communities with high levels of HIV, TB and poverty decreased similar to global experiences however there was no change in in-hospital mortality. No post-pandemic surge in admissions or mortality were documented. Differences in the impact of pandemic control measures on transmission of childhood infections and access to health care may account for differing outcomes seen in our setting compared to the global experiences. Further studies are needed to understand the impact of pandemic control measures on healthcare provision and transmission dynamics and to better inform future responses amongst vulnerable child populations.

Mild and moderate COVID-19 during Alpha, Delta and Omikron pandemic waves in urban Maputo, Mozambique, December 2020-March 2022: a population-based surveillance study (preprint)

In sub-Saharan Africa, reported COVID-19 numbers have been lower than anticipated, even when considering populations younger age. The extent to which risk factors, established in industrialised countries, impact the risk of infection and of disease in populations in sub-Saharan Africa, remains unclear. We estimated the incidence of mild and moderate COVID-19 in urban Mozambique and analysed factors associated with infection and disease in a population-based surveillance study. During December 2020-March 2022, households of a population cohort in Polana Canico, Maputo, Mozambique, were contacted biweekly. Residents reporting any respiratory sign, anosmia, or ageusia, were asked to self-administer a nasal swab, for SARS-CoV-2 PCR testing. Of a subset of 1400 participants, dried blood spots were repeatedly collected three-monthly from finger pricks at home. Antibodies against SARS-CoV-2 spike glycoprotein and nucleocapsid protein were detected using an in-house developed multiplex antibody assay. We estimated the incidence of respiratory illness and COVID-19, and SARS-CoV-2 seroprevalence. We used Cox regression models, adjusting for age and sex, to identify factors associated with first symptomatic COVID-19 and with SARS-CoV-2 sero-conversion in the first six months. During 11925 household visits in 1561 households, covering 6049 participants (median 21 years, 54.8% female, 7.3% disclosed HIV positive), 1895.9 person-years were followed up. Per 1000 person-years, 364.5 (95%CI 352.8-376.1) respiratory illness episodes of which 72.2 (95%CI 60.6-83.9) COVID-19 confirmed, were reported. Of 1412 participants, 2185 blood samples were tested (median 30.6 years, 55.2% female). Sero-prevalence rose from 4.8% (95%CI 1.1-8.6%) in December 2020 to 34.7% (95%CI 20.2-49.3%) in June 2021, when 3.0% were vaccinated. Increasing age (strong gradient in hazard ratio, HR, up to 15.70 in [≥]70 year olds, 95%CI 3.74-65.97), leukaemia, chronic lung disease, hypertension, and overweight increased risk of COVID-19. We found no increased risk of COVID-19 in people with HIV or tuberculosis. Risk of COVID-19 was lower among residents in the lowest socio-economic quintile (HR 0.16, 95%CI 0.04-0.64), with no or limited handwashing facilities, and who shared bedrooms (HR 0.42, 95%CI 0.25-0.72). Older age also increased the risk of SARS-CoV-2 seroconversion (HR 1.57 in 60-69 year olds, 95%CI 1.03-2.39). We found no associations between SARS-CoV-2 infection risk and socio-economic, behavioural factors and comorbidities. Active surveillance in an urban population cohort confirmed frequent COVID-19 underreporting, yet indicated that the large majority of cases were mild and non-febrile. In contrast to industrialised countries, deprivation did not increase the risk of infection nor disease.

A qualitative exploration of the impact of the COVID-19 pandemic on gender-based violence against women living with HIV or tuberculosis in Timor Leste (preprint)

Violence against women or gender-based violence (GBV) is a major public health issue facing women and girls in different settings and is reported to have worsened globally during the COVID-19 pandemic. Despite the impact of the COVID-19 pandemic on increased violence against women in general, which has been reported in many settings globally, there is a paucity of evidence of its impact on violence against highly vulnerable women living with HIV or tuberculosis (TB). Using a qualitative design, this study aimed to explore the views and experiences of women living with HIV (n=19) or TB (n=23) in Timor Leste regarding the GBV they faced during the COVID-19 pandemic. They were recruited using the snowballing sampling technique. Data were collected using one-on-one in-depth interviews and focus group discussions. The five steps of qualitative data analysis suggested in Ritchie and Spencer’s analysis framework were employed to guide the analysis of the findings. Findings indicated that women in this study experienced intensified physical, verbal, sexual and psychological violence by their partners, spouses, in-laws, and parents or other family members during the COVID-19 pandemic. Several prominent risk factors that worsened violence against women during the pandemic were (i) HIV or TB-positive status, (ii) traditional gender roles or responsibilities and expectations, (iii) economic and financial difficulties reflected in the loss of jobs and incomes due to the pandemic, and (iv) individual factors such as jealousy and increased alcohol drinking developed during the lockdowns. The findings underscore the urgent need for multifaceted interventions to address GBV, which should encompass challenging traditional gender norms, addressing economic inequalities, and targeting individual-level risk factors. The findings also indicate the need for the development of robust monitoring and evaluation systems to assess the effectiveness of policies and interventions addressing GBV where the results can inform future improvement. The findings also indicate the need to include GBV in the protocol or guidelines for HIV and TB management. Future large-scale quantitative studies to capture the magnitude and specific drivers of GBV against women living with HIV and TB during the pandemic are recommended.

Sex disparities of the effect of the COVID-19 pandemic on mortality among patients living with tuberculosis in the United States (preprint)

Background： We aimed to determine the trend of tuberculosis (TB)-related deaths during the pandemic, with focus on the impact of the epidemic on mortality in males and females. Methods： Using data from the Centers for Disease Control and Prevention and the U.S. Census Bureau, TB-related mortality data of decedents aged ≥ 25 years from 2006-2021 were analyzed. Excess TB-related deaths were estimated by determining the difference between observed and projected mortality rates during the pandemic. The mortality trends were then quantified with Joinpoint regression analysis. Results： A total of 18,626 TB-related deaths were documented among adults aged 25 years and older from 2006-2021. A downward trend was noted in TB-related mortality rates before the pandemic, followed by an increase during the pandemic. TB-related age-standardized mortality rates (ASMRs) were 0.51 in 2020 and 0.52 in 2021, corresponding to an excess mortality of 10.22% and 9.19%, respectively. Increased TB-related mortality was observed across all age and sex subgroups, but female with TB demonstrated a higher relative increase in mortality (26.33% vs. 2.17% in 2020; 21.48% vs.3.23% in 2021) during the pandemic when compared to male. Furthermore, female with TB and aged 45-64 years old showed a surge in mortality, with an annual percent change (APC) of -2.2% pre-pandemic to 22.8% (95% CI: -1.7% to 68.7%) during the pandemic, corresponding to excess mortalities of 62.165% and 99.16% in 2020 and 2021, respectively; these excess mortality rates were higher than those observed in the overall female population ages 45-64 years in 2020 (17.53%) and 2021 (33.79%). Conclusions： The steady decline in TB-related mortality in the United States has been reversed by COVID-19. Female patients with TB were disproportionately affected by the pandemic, largely owing to care gaps and health disparities experienced by this population.

Clinical pattern and diagnostic of comorbidity of respiratory tuberculosis and viral pneumonia caused by Herpesvirus Simplex, Human Cytomegalovirus and SARS-CoV-2 in patients with late-stage HIV infection with immunodeficiency (preprint)

Aim. To study features of social status, clinical pattern and diagnosis in cases of comorbidity of respiratory tuberculosis and viral pneumonia caused by Herpesvirus Simplex of type 1, Human Cytomegalovirus and SARS-CoV-2 in patients with late-stage HIV infection with immunodeficiency. Materials and methods. The prospective study included 25 patients with comorbid condition of respiratory tuberculosis with Mycobacterium tuberculosis in excreta, herpesvirus and coronavirus pneumonia, and 21 patients with respiratory tuberculosis as well as cytomegalovirus and coronavirus pneumonia (1a and 2a main groups) and, respectively, 25 and 21 similar patients, but without coronavirus pneumonia (1b and 2b comparison group) in the late stages of HIV infection with immunodeficiency. For the etiological diagnosis of herpesvirus and cytomegalovirus pneumonia, the PCR test was used for recognition of DNA of Herpesvirus Simplex of type 1 and Human Cytomegalovirus in the diagnostic material of respiratory tract and for the etiological diagnosis of coronavirus pneumonia, the PCR for recognition of RNA was used to reveal SARS-CoV-2. Statistical analysis of the data was performed by the use of the Microsoft Office Excel 2019 software for calculation of group mean, standard error of mean and confidence interval. Results. The comorbidity of respiratory tuberculosis, herpes-, cytomegalo- and coronavirus pneumonia in patients with late-stage HIV infection in the phase of progression and in the absence of ART was characterized by severe immunodeficiency and generalization of tuberculosis with multiple extrapulmonary lesions. The results displayed similarity of clinical manifestations and visualization of changes in CT-picture in cases of comorbidity the diseases which hampers their recognition due to simultaneous combination of several pathologies with similar clinical manifestations that requires a complex etiological diagnosis of the specific diseases to prescribe a timely comprehensive treatment and reduce lethality in this severe contingent of patients. Conclusion. Patients with respiratory tuberculosis and HIV infection registered in the office of tuberculosis care for HIV-infected individuals in the antituberculosis dispensary represent a group of high risk from COVID-19 infection and CVP disease, and, in cases of combination with severe immunodeficiency, HVP and CMVP, the patients should be regularly subjected to preventive studies for timely detection of COVID-19 for the purpose of their emergency isolation and treatment.

Molecular Property Diagnostic Suite for COVID-19 (MPDSCOVID-19): An open access disease specific drug discovery portal (preprint)

Computational drug discovery is intrinsically interdisciplinary and has to deal with the multifarious factors which are often dependent on the type of disease. Molecular Property Diagnostic Suite (MPDS) is a Galaxy based web portal which was conceived and developed as a disease specific web portal, originally developed for tuberculosis (MPDSTB). As specific computational tools are often required for a given disease, developing a disease specific web portal is highly desirable. This paper emphasises on the development of the customised web portal for COVID-19 infection and is referred to as MPDSCOVID-19. Expectedly, the MPDS suites of programs have modules which are essentially independent of a given disease, whereas some modules are specific to a particular disease. In the MPDSCOVID-19 portal, there are modules which are specific to COVID-19, and these are clubbed in SARS-COV-2 disease library. Further, the new additions and/or significant improvements were made to the disease independent modules, besides the addition of tools from galaxy toolshed. This manuscript provides a latest update on the disease independent modules of MPDS after almost 6 years, as well as provide the contemporary information and tool-shed necessary to engage in the drug discovery research of COVID-19. The disease independent modules include file format converter and descriptor calculation under the data processing module; QSAR, pharmacophore, scaffold analysis, active site analysis, docking, screening, drug repurposing tool, virtual screening, visualisation, sequence alignment, phylogenetic analysis under the data analysis module; and various machine learning packages, algorithms and in-house developed machine learning antiviral prediction model are available. The MPDS suite of programs are expected to bring a paradigm shift in computational drug discovery, especially in the academic community, guided through a transparent and open innovation approach. The MPDSCOVID-19 can be accessed at http://mpds.neist.res.in:8085.

The impact of COVID-19 Pandemic on Domestic Gender Based Violence Against Female HIV and Tuberculosis Patients in Timor-Leste: A Qualitative Study (preprint)

Abstract: Context: Globally, there is still widespread of violence against women and girls. Timor-Leste reports high prevalence of GBV with 30% women have experienced intimate partner (IPV) or non-partner sexual violence. Several studies reported about the increase of domestic violence gender-based violence (D-GBV) against girls and women worldwide during the COVID-19 pandemic. Aims: To understand whether women living with these two diseases experienced D- GBV during the lockdowns in Timor-Leste. Methods and Material: The study was a qualitative phenomenology design, utilizing purposive sampling technic. Was conducted in eight municipalities from early October 2022 to end of February 2023. It considered eight independent variables to identified the occurrence of D-GBV. Subject 42 in-depth interviews: 19 HIV, 23 TB participants, and 3 FGDs. Data analysis with NVIVO version 12.1. Results: The D- GBV were widely reported from all municipalities. Psychological, socio-economic, verbal, and physical violence were mostly reported. The COVID-19 pandemic exacerbated D- GBV, and impeded participants to apply coping mechanisms in dealing with the violence. Stigma and discrimination were prevalent. The main causes of the violence were economic factors, jealousy, denial, cultural issues, and failure to perform household work. The participants reported using various coping mechanisms to deal with D- GBV: seeking external support or avoidance and staying, facing the perpetrator at home. Conclusions: The triple vulnerabilities (weaknesses of system to combat D-GBV, stigma, discrimination against female TB and HIV patients. It is recommended to train clinician working on D-GBV subject.

Impact of COVID-19 on the cascade of care for tuberculosis: A systematic review (preprint)

ObjectivesTo describe the impact of the COVID-19 pandemic on the TB care cascade. MethodsIn this systematic review, the Cochrane library, Scopus, CINAHL, Ebscohost, and PubMed databases were comprehensively searched from the onset of the pandemic, till May 5th, 2022. Eligible studies were those reporting on changes in the TB cascade of care one year before and one year during the COVID-19 pandemic. Due to the expected differences in the contexts of the included studies, a narrative synthesis was conducted. ResultsTwenty-seven studies, from Asia, North America, Africa, South America, and Europe were included. TB screening decreased by between 1% - 50%, and multidrug resistance tuberculosis (MDR-TB) screening decreased by between 15%-17%. Diagnostic delay increased by between 35 - 45 days, contact tracing decreased by up to 36.1%, and case notification decreased by between 3%-63%. TB treatment enrolment decreased by between 16%-35.0%, treatment completion decreased by around 8.0% and treatment success decreased by up to 17.0%. ConclusionCOVID-19 had a detrimental impact on the TB care cascade and these findings suggest a need for policies to protect healthcare systems for TB and other communicable diseases in future health emergencies. Protocol registration - PROSPERO: CRD42021272456 Ethics approvalThis systematic review used data from published studies and aggregated data, thus, ethics approval was not required.

Impact of COVID-19 prevention and control on tuberculosis and scarlet fever in China's Guizhou.

China has implemented a series of long-term measures to control the spread of COVID-19, however, the effects of these measures on other chronic and acute respiratory infectious diseases remain unclear. Tuberculosis (TB) and scarlet fever (SF) serve as representatives of chronic and acute respiratory infectious diseases, respectively. In China's Guizhou province, an area with a high prevalence of TB and SF, approximately 40,000 TB cases and hundreds of SF cases are reported annually. To assess the impact of COVID-19 prevention and control on TB and SF in Guizhou, the exponential smoothing method was employed to establish a prediction model for analyzing the influence of COVID-19 prevention and control on the number of TB and SF cases. Additionally, spatial aggregation analysis was utilized to describe spatial changes in TB and SF before and after the COVID-19 outbreak. The parameters of the TB and SF prediction models are R2 = 0.856, BIC = 10.972 and R2 = 0.714, BIC = 5.325, respectively. TB and SF cases declined rapidly at the onset of COVID-19 prevention and control measures, with the number of SF cases decreasing for about 3-6 months and the number of TB cases remaining in decline for 7 months after the 11th month. The spatial aggregation of TB and SF did not change significantly before and after the COVID-19 outbreak but exhibited a marked decrease. These findings suggest that China's COVID-19 prevention and control measures also reduced the prevalence of TB and SF in Guizhou. These measures may have a long-term positive impact on TB, but a short-term effect on SF. Areas with high TB prevalence may continue to experience a decline due to the implementation of COVID-19 preventive measures in the future.

Optimising the yield from bronchoalveolar lavage on human participants in infectious disease immunology research.

Bronchoalveolar lavage (BAL) is becoming a common procedure for research into infectious disease immunology. Little is known about the clinical factors which influence the main outcomes of the procedure. In research participants who underwent BAL according to guidelines, the BAL volume yield, and cell yield, concentration, viability, pellet colour and differential count were analysed for association with important participant characteristics such as active tuberculosis (TB) disease, TB exposure, HIV infection and recent SARS-CoV-2 infection. In 337 participants, BAL volume and BAL cell count were correlated in those with active TB disease, and current smokers. The right middle lobe yielded the highest volume. BAL cell and volume yields were lower in older participants, who also had more neutrophils. Current smokers yielded lower volumes and higher numbers of all cell types, and usually had a black pellet. Active TB disease was associated with higher cell yields, but this declined at the end of treatment. HIV infection was associated with more bloody pellets, and recent SARS-CoV-2 infection with a higher proportion of lymphocytes. These results allow researchers to optimise their participant and end assay selection for projects involving lung immune cells.

Individual healthcare-seeking pathways for tuberculosis in Nigeria private sector during the COVID-19 pandemic (preprint)

Background: Pre-COVID-19, individuals with TB in Nigeria were often underdiagnosed and untreated. Care for TB was mostly in the public sector while only 15% of new cases in 2019 were from the private sector. Reports highlighted challenges in accessing care in the private sector, which accounted for 67% of all initial care-seeking. Our study examined patients health seeking pathways for TB in Nigeria private sector, and explored any changes to care pathways during COVID, based on patients perspectives. Design/Methods: We conducted 180 cross-sectional surveys and 20 in-depth interviews with individuals having chest symptoms attending 18 high volume private clinics and hospitals in Kano and Lagos States. Questions focused on sociodemographic characteristics, health-seeking behavior and pathways to care during the COVID-19 periods. All surveys and interviews were conducted in May 2021. Results: Most participants were male (n=111, 62%), with average age of 37. Half (n=96, 53.4%) sought healthcare within a week of symptoms, while few (n=20, 11.1%) waited over 2 months. TB positive individuals had more health-seeking delays, and TB negative had more provider delays. On average, participants visited 2 providers in Kano and 1.69 in Lagos, with 61 (75%) in Kano and 48 (59%) in Lagos visiting other providers before the recruitment facility. Private providers were the initial encounters for most participants (n=60 or 66.7% in Kano, n-83 or 92.3% in Lagos). Most respondents (164 or 91%) experienced short-lived pandemic-related restrictions, particularly during the lockdowns, affecting access to transportation, and closed facilities. Conclusions: This study showed a few challenges in accessing TB healthcare in Nigeria, necessitating continued investment in healthcare infrastructure and resources, particularly in the private sector. Understanding the different care pathways and delays in care provides opportunities for targeted interventions to improve deployment of services closer to where patients first seek care.