Infectious Killer Research Articles

A nomogram for predicting mortality of patients initially diagnosed with primary pulmonary tuberculosis in Hunan province, China: a retrospective study.

According to the Global Tuberculosis Report for three consecutive years, tuberculosis (TB) is the second leading infectious killer. Primary pulmonary tuberculosis (PTB) leads to the highest mortality among TB diseases. Regretfully, no previous studies targeted the PTB of a specific type or in a specific course, so models established in previous studies cannot be accurately feasible for clinical treatments. This study aimed to construct a nomogram prognostic model to quickly recognize death-related risk factors in patients initially diagnosed with PTB to intervene and treat high-risk patients as early as possible in the clinic to reduce mortality. We retrospectively analyzed the clinical data of 1,809 in-hospital patients initially diagnosed with primary PTB at Hunan Chest Hospital from January 1, 2019, to December 31, 2019. Binary logistic regression analysis was used to identify the risk factors. A nomogram prognostic model for mortality prediction was constructed using R software and was validated using a validation set. Univariate and multivariate logistic regression analyses revealed that drinking, hepatitis B virus (HBV), body mass index (BMI), age, albumin (ALB), and hemoglobin (Hb) were six independent predictors of death in in-hospital patients initially diagnosed with primary PTB. Based on these predictors, a nomogram prognostic model was established with high prediction accuracy, of which the area under the curve (AUC) was 0.881 (95% confidence interval [Cl]: 0.777-0.847), the sensitivity was 84.7%, and the specificity was 77.7%.Internal and external validations confirmed that the constructed model fit the real situation well. The constructed nomogram prognostic model can recognize risk factors and accurately predict the mortality of patients initially diagnosed with primary PTB. This is expected to guide early clinical intervention and treatment for high-risk patients.

Knowledge and Healthcare Seeking Behavior among Tuberculosis Patients Attending Some Selected Tuberculosis Centers in Mogadishu, Somalia

Introduction: Tuberculosis is a disease caused by Mycobacterium tuberculosis germs. The bacteria are most commonly found in the lungs but can also harm other sections of the body. Worldwide about 1.5 million people died from tuberculosis (TB) in 2020 (including 214 000 people with HIV). TB is the 13th leading cause of death worldwide and the second leading infectious killer after COVID-19 (above HIV/AIDS). This study aims to determine TB patients' knowledge and healthcare-seeking behavior attending Mogadishu- Somalia, in some selected TB centers. Methods: A cross-sectional study was conducted among tuberculosis patients in five TB management units in Mogadishu, Somalia. The data collection tools used to collect data were close-ended self-administrated questionaries from May to June 2022. The target population of this study was TB patients registered and taking treatment during data collection. The sample size of this study was 384 respondents. We used logistic regression analysis to identify the factors associated with knowledge about TB and healthcare-seeking behavior among TB patients. Results: The study found that the mean score for all knowledge of tuberculosis was 22.7. 209 (54.4%) of the 384 TB patients had good knowledge of the disease, compared to 175 (45.6%) who had poor knowledge. The average score for TB patients' healthcare-seeking behavior was 6.67. 200(52.1%) of the 384 respondents reported good healthcare-seeking behavior about TB, compared to 184 (47.9%) of the respondents who had bad healthcare-seeking behavior Conclusion: TB patients had good knowledge of the signs and symptoms of TB, the transmission of TB, treatment of TB, and healthcare-seeking behavior of TB, but their knowledge of the cause of TB and the method of prevention of TB was not adequate. This study also revealed that the healthcare-seeking behavior of TB patients was good.

CORRELATION BETWEEN POPULATION DENSITY, CURE RATE, MORTALITY RATE WITH TB AFB+ INCIDENCE IN SURABAYA 2018-2020

Background: In 2020, the World Health Organization (WHO) stated that as many as 10 million people suffered from tuberculosis and 1.5 million died, making it the 13th cause of death in the world's top infectious killer number two after COVID-19. The incidence of Acid-fast bacillus (AFB)+ Tuberculosis TB in Surabaya increased from 2018 to 2020. Purpose: This study aimed to describe the distribution of TB AFB+ incidence in Surabaya by mapping and to analyze the relationship between population density, TB AFB+ cure rates, and death rates during TB AFB+ treatment with AFB + TB incidence in 31 sub-districts of Surabaya City from 2018 to 2020. Methods: This was a descriptive study with secondary data processing obtained from the Surabaya Health Profile Book 2018-2020 using the Pearson Correlation Product Moment statistical test. Results: There was a correlation between population density and the incidence of TB AFB+ in 2018 (0.61), 2019 (0.65), and 2020 (0.62). Then there was a correlation between TB AFB+ cure rate and TB AFB+ incidence in 2018 (0.98), 2019 (0.96), and 2020 (0.91). There was a correlation between the mortality rate during TB AFB+ treatment and the incidence of TB AFB+ in 2018 (0.31), 2019 (0.71), and 2020 (0.88). Conclusion: There is a relationship between population density, TB AFB + cure rate, the mortality rate during AFB + TB treatment, and the incidence of AFB + TB in Surabaya.

Beneficial or detrimental activity of regulatory T cells, indoleamine 2,3-dioxygenase, and heme oxygenase-1 in the lungs is influenced by the level of virulence of Mycobacterium tuberculosis strain infection.

Tuberculosis (TB) caused by the complex Mycobacterium tuberculosis (Mtb) is the main cause of death by a single bacterial agent. Last year, TB was the second leading infectious killer after SARS-CoV-2. Nevertheless, many biological and immunological aspects of TB are not completely elucidated, such as the complex process of immunoregulation mediated by regulatory T cells (Treg cells) and the enzymes indoleamine 2,3-dioxygenase (IDO) and heme oxygenase 1 (HO-1). In this study, the contribution of these immunoregulatory factors was compared in mice infected with Mtb strains with different levels of virulence. First Balb/c mice were infected by intratracheal route, with a high dose of mild virulence reference strain H37Rv or with a highly virulent clinical isolate (strain 5186). In the lungs of infected mice, the kinetics of Treg cells during the infection were determined by cytofluorometry and the expression of IDO and HO-1 by RT-PCR and immunohistochemistry. Then, the contribution of immune-regulation mediated by Treg cells, IDO and HO-1, was evaluated by treating infected animals with specific cytotoxic monoclonal antibodies for Treg cells depletion anti-CD25 (PC61 clone) or by blocking IDO and HO-1 activity using specific inhibitors (1-methyl-D,L-tryptophan or zinc protoporphyrin-IX, respectively). Mice infected with the mild virulent strain showed a progressive increment of Treg cells, showing this highest number at the beginning of the late phase of the infection (28 days), the same trend was observed in the expression of both enzymes being macrophages the cells that showed the highest immunostaining. Animals infected with the highly virulent strain showed lower survival (34 days) and higher amounts of Treg cells, as well as higher expression of IDO and HO-1 one week before. In comparison with non-treated animals, mice infected with strain H37Rv with depletion of Treg cells or treated with the enzymes blockers during late infection showed a significant decrease of bacilli loads, higher expression of IFN-g and lower IL-4 but with a similar extension of inflammatory lung consolidation determined by automated morphometry. In contrast, the depletion of Treg cells in infected mice with the highly virulent strain 5186 produced diffuse alveolar damage that was similar to severe acute viral pneumonia, lesser survival and increase of bacillary loads, while blocking of both IDO and HO-1 produced high bacillary loads and extensive pneumonia with necrosis. Thus, it seems that Treg cells, IDO and HO-1 activities are detrimental during late pulmonary TB induced by mild virulence Mtb, probably because these factors decrease immune protection mediated by the Th1 response. In contrast, Treg cells, IDO and HO-1 are beneficial when the infection is produced by a highly virulent strain, by regulation of excessive inflammation that produced alveolar damage, pulmonary necrosis, acute respiratory insufficiency, and rapid death.

Cell painting assays for profiling responses in Mycobacterium tuberculosis-infected macrophages after metabolic perturbation

Abstract Tuberculosis (TB) is the leading infectious disease killer in the world, and a lack of accessible, easy treatments contributes to its growing burden. Repurposing approved treatments for other conditions, including metabolic inhibitors under consideration for use in cancer therapy, as host-directed therapies may improve TB treatments. Detailed preliminary studies to identify mechanisms that underly drug function need to be performed before these drugs can be used in patients but there is a lack of tools to investigate metabolic perturbations in target cells. This problem is particularly acute for treatments that have uncharacterized effects on host cells or host-pathogen interactions, or for adherent cells where cell morphology and migration patterns may be factors that are modulated by treatments. Cell painting assays are microscopy-based analyses that use quantitative imaging data to generate insight into how drugs and infections perturb host cells. Here, we sought to optimize a cell painting assay to investigate changes in macrophage morphology and antimicrobial activity after metabolic perturbation and Mycobacterium tuberculosis(Mtb) infection. Our objective was to apply the quantification and analysis pipelines to macrophages that were infected with fluorescent Mtb reporter strains to identify cellular responses after inhibition of fatty acid oxidation, oxidative phosphorylation, or glycolysis. Moreover, we compared inhibitors that target different points in the glycolysis pathway to define how these points differentially affect macrophage antimicrobial activity. Our work provides a framework for using cell painting assays as tools for dissecting host-pathogen interactions in metabolically perturbed cells. Supported by grants from NIH grants AI167710 and #LINK#AI164970#ENDLINK#

Mycobacterial metabolic model development for drug target identification.

Antibiotic resistance is increasing at an alarming rate, and three related mycobacteria are sources of widespread infections in humans. According to the World Health Organization, Mycobacterium leprae, which causes leprosy, is still endemic in tropical countries; Mycobacterium tuberculosis is the second leading infectious killer worldwide after COVID-19; and Mycobacteroides abscessus, a group of non-tuberculous mycobacteria, causes lung infections and other healthcare-associated infections in humans. Due to the rise in resistance to common antibacterial drugs, it is critical that we develop alternatives to traditional treatment procedures. Furthermore, an understanding of the biochemical mechanisms underlying pathogenic evolution is important for the treatment and management of these diseases. In this study, metabolic models have been developed for two bacterial pathogens, M. leprae and My. abscessus, and a new computational tool has been used to identify potential drug targets, which are referred to as bottleneck reactions. The genes, reactions, and pathways in each of these organisms have been highlighted; the potential drug targets can be further explored as broad-spectrum antibacterials and the unique drug targets for each pathogen are significant for precision medicine initiatives. The models and associated datasets described in this paper are available in GigaDB, Biomodels, and PatMeDB repositories.

RR-TB treatments, testing bedaquiline and injectable kanamycin

RR-TB treatments, testing bedaquiline and injectable kanamycin Here, Professor Andre Nunn from Medical Research Council Clinical Trials Unit at UCL, explores tuberculosis with a focus on RR-TB treatments (rifampicin-resistant) and their drug combinations. Tuberculosis (TB) is one of the oldest diseases known to man and its management remains a challenge to public health worldwide. According to the most recent World Health Organisation (WHO) report over 10 million persons fell ill with tuberculosis in 2021. It occurs within all the countries of the world but is most prevalent in low and middle income countries. A total of 1.6 million people died from TB world-wide in 2021 making it the 13th leading cause of death and the second leading infectious disease killer after COVID-19.

Tuberculosis vaccines update: Is an RNA-based vaccine feasible for tuberculosis?

ObjectivesDespite concerted efforts, Mycobacterium tuberculosis (M.tb), the pathogen that causes tuberculosis (TB), continues to be a burden on global health, regaining its dubious distinction in 2022 as the world's biggest infectious killer with global COVID-19 deaths steadily declining. The complex nature of M.tb, coupled with different pathogenic stages, has highlighted the need for the development of novel immunization approaches to combat this ancient infectious agent. Intensive efforts over the last couple of decades have identified alternative approaches to improve upon traditional vaccines that are based on killed pathogens, live attenuated agents, or subunit recombinant antigens formulated with adjuvants. Massive funding and rapid advances in RNA-based vaccines for immunization have recently transformed the possibility of protecting global populations from viral pathogens, such as SARS-CoV-2. Similar efforts to combat bacterial pathogens such as M.tb have been significantly slower to implement. MethodsIn this review, we discuss the application of a novel replicating RNA (repRNA)-based vaccine formulated and delivered in nanostructured lipids. ResultsOur preclinical data are the first to report that RNA platforms are a viable system for TB vaccines and should be pursued with high-priority M.tb antigens containing cluster of differentiation (CD4+) and CD8+ T-cell epitopes. ConclusionThis RNA vaccine shows promise for use against intracellular bacteria such as M.tb as demonstrated by the feasibility of construction, enhanced induction of cell-mediated and humoral immune responses, and improved bacterial burden outcomes in in vivo aerosol-challenged preclinical TB models.

Spatial Distribution of Drug-Resistant Mycobacterium tuberculosis Infections in Rural Eastern Cape Province of South Africa.

Tuberculosis (TB), an infectious airborne disease caused by Mycobacterium tuberculosis (Mtb), is a serious public health threat reported as the leading cause of morbidity and mortality worldwide. South Africa is a high-TB-burden country with TB being the highest infectious disease killer. This study investigated the distribution of Mtb mutations and spoligotypes in rural Eastern Cape Province. The Mtb isolates included were 1157 from DR-TB patients and analysed by LPA followed by spoligotyping of 441 isolates. The distribution of mutations and spoligotypes was done by spatial analysis. The rpoB gene had the highest number of mutations. The distribution of rpoB and katG mutations was more prevalent in four healthcare facilities, inhA mutations were more prevalent in three healthcare facilities, and heteroresistant isolates were more prevalent in five healthcare facilities. The Mtb was genetically diverse with Beijing more prevalent and largely distributed. Spatial analysis and mapping of gene mutations and spoligotypes revealed a better picture of distribution.

Strengthened primary health care for universal health coverage through improved community diagnosis and management of pneumonia in Zimbabwe

Pneumonia is the world’s leading infectious killer, claiming the lives of an estimated 2.5 million including more than 670,000 children under five years and 1.2 million adults in 2019 alone. Caused largely by viruses, and bacteria, COVID-19 also increased the pneumonia burden, while environmental factors, poor hygiene, sanitation and underlying conditions including malnutrition predispose. The latter translates into a considerable pneumonia burden that is preventable, provided the requisite provisions are made for community-level protection such as environmental management, water, sanitation and hygiene; and key persons are informed and educated on preventive and therapeutic measures, especially what to look for and what to do at home while seeking medical attention. Irked by the high numbers of under-five deaths against a background of limited case management caused by the system-wide collapse of the health services in the country, we sought to utilize the opportunity offered by world pneumonia day 2022 to go down to the community and elicit both the disease burden and strategies to address pneumonia that can be applied within the home and community. We also wanted to hear from the community their experiences with and functionality of the referral system. This paper presents the findings, challenges and suggestions for improving primary healthcare implementation to address the current high morbidity and mortality attributable to pneumonia. We found the Goromonzi community to be literate in many health issues but need more information and training to better manage pneumonia. They were knowledgeable about pneumonia, tuberculosis, and the recent COVID-19 through their interactions with the local clinic staff, the media, and interpersonal communication. Some were members of the health center committee or were village health workers or local leaders. We had limitations of resources and time for a detailed study, but conclude that the community visited had a sound understanding of health, primary health care and pneumonia, but lacked the comprehensive education and support to effectively manage pneumonia at home. More work needs to be done to quantify the pneumonia burden, the contribution of each intervention, (environment, vaccination, exclusive breastfeeding, safe water, sanitation, hand hygiene, reduced smoke and case management) the benefit of home and community management alongside an effective referral chain.

Structure-function analysis of the dual functioning mycobacterial virulence factors EspE and EspF.

Mycobacterium tuberculosis is the world's second leading infectious disease killer, with approximately 1.5 million people succumbing to the disease annually. Protein export by the ESX-1 secretion system is essential for the virulence of pathogenic mycobacteria, including M. tuberculosis and nontuberculous mycobacteria (NTMs) such as Mycobacterium marinum. ESX-1 mediates rupture of the phagosomal membrane, allowing mycobacteria to gain access to the cytoplasm of host macrophages. Phagosomal lysis is required for host cell death and mycobacterial cell-to-cell spread. Our previous work demonstrated that the ESX-1 substrates EspE and EspF are required for the membranolytic activity of M. marinum. Our lab recently showed that EspE and EspF are the last set of substrates secreted by the ESX-1 system and require each other for secretion. Moreover, EspE and EspF regulate gene expression in the mycobacterial cytoplasm. Using a targeted genetic approach, we are conducting a structure-function analysis to determine if protein interaction is required for the hemolytic and regulatory activities of EspE and EspF. We show that the disruption of a predicted salt bridge between EspE and EspF abrogates hemolytic activity and EspE secretion. In addition, the protein-protein interface between EspF and EsxA is necessary for hemolytic activity. Disruption of this region leads to a substantial decrease in EspE secretion. This, combined with EsxB secretion data, shows that EspE-EspF interaction is required for secretion, but may not be required for gene regulation. These data provide new insight into the unique ESX-1 substrates EspE and EspF in gene regulation, protein secretion, and virulence.

Re-evaluating the Role of Antibodies in Tuberculosis

Tuberculosis (TB) is a disease found in every country on Earth. About a quarter of the global population is estimated to be infected with Mycobacterium tuberculosis, the causative agent of TB, with over 10 million new TB cases reported annually. Currently, TB ranks as the second leading infectious killer after COVID-19. Research to develop novel interventions against TB represents a global health priority. TB research over the last several years focused on cellular immune responses, while the humoral response was largely neglected. This mini-review discusses evidence supporting a protective role of antibodies in TB, and a potential role of antibodies in TB vaccines and diagnosis.

Association of IFN-γ +874 A/T SNP and hypermethylation of the -53 CpG site with tuberculosis susceptibility.

Tuberculosis (TB) is now the 2nd leading infectious killer after COVID-19 and the 13th leading cause of death worldwide. Moreover, TB is a lethal combination for HIV-patients. Th1 responses and particularly IFN-γ are crucial for immune protection against Mycobacterium tuberculosis infection. Many gene variants for IFNG that confer susceptibility to TB have been described in multiple ethnic populations. Likewise, some epigenetic modifications have been evaluated, being CpG methylation the major epigenetic mark that makes chromatin inaccessible to transcription factors, thus avoiding the initiation of IFNG transcription. We evaluated both genetic and epigenetic changes involved in IFN-γ production and TB susceptibility in Argentine population. Amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) was performed for the IFN-γ +874 A/T polymorphism (rs2430561) genotyping in 199 healthy donors (HD) and 173 tuberculosis (TB) patients. IFN-γ levels from M. tuberculosis-stimulated PBMCs were measured by ELISA. The methylation status at the -53 CpG site of the IFNG promoter in individuals with latent infection (LTBI), TB and HD was determine by pyrosequencing. Using a case-control study, we found that A allele and, consequently, AA genotype were overrepresented in patients with active disease. Moreover, HD carrying T allele (AT or TT genotype) evidenced an augmented IFN-γ secretion compared to TB patients. Codominance was the genetic model that best fits our results according to the Akaike information criterion (AIC). In addition, increased methylation levels at the -53 CpG site in the IFN-γ promoter were observed in whole blood of patients with active TB compared to LTBI individuals. IFN-γ is regulated by genetic variants and epigenetic modifications during TB. Besides, AA genotype of the rs2430561 single nucleotide polymorphism could be considered as a potential TB susceptibility genetic biomarker in Argentina and the methylation of the -53 CpG site could result in a useful predictor of TB reactivation.

ASSESSING THE PREVALENCE OF DIABETES MELLITUS (DM) AND HIV AMONG THE NOTIFIED TUBERCULOSIS (TB) IN A DISTRICT OF NORTH INDIA: A SECONDARY DATA ANALYSIS.

ntroduction:Tuberculosis (TB) is the largest infectious disease killer in the world.The double burden of TB and DM has recently emerged as an important public health problem in India highlighting the importance of screening TB patients for DM on a routine basis.The importance of HIV surveillance in TB patients is increasingly being realized as the HIV epidemic continues to fuel the global TB epidemic.This study was planned with the main objective of determining the prevalence of DM and HIV among TB patients.Materials and methods:It was an institutional based study with secondary data analysis of first quarter (January -March 2022) notified cases of Tuberculosis in District Kullu, Himachal Pradesh. Data collected was coded and then entered in Microsoft-excel spreadsheet and was analysed using SPSS version 24. Results:Prevalence of Diabetes Mellitus (DM) and HIV among the TB cases was found to be 3.4% and 0.3% respectively. Also,type of TB was not found to be significantly associated with any characterstic of the patients.Conclusion:The actual count may be much higher, so rigrous screening for DM and HIV among TB patients is need of every hour so that better treatment outcomes are achieved.

Prevalence and molecular characterization of Mycobacterium tuberculosis complex in cattle and humans, Maiduguri, Borno state, Nigeria: a cross-sectional study

IntroductionGlobally, the highest burden of bovine and human tuberculosis resides in Africa and Asia. Tuberculosis (TB) is the second leading single infectious killer after severe acute respiratory syndrome corona virus-2 (SARSCOV-2). Bovine TB remains a treat to wild and domesticated animals, humans and hinders international trade in endemic countries like Nigeria. We aimed at determining the prevalence of bovine and human tuberculosis, and the spoligotypes of Mycobacterium tuberculosis complex in cattle and humans in Maiduguri.MethodsWe conducted a cross sectional study on bovine and human tuberculosis in Maiduguri, Borno state. We calculated sample size using the method of Thrusfield. Lesions suggestive of TB from 160 slaughtered cattle were obtained from Maiduguri Central Abattoir. Sputum samples from humans; 82 abattoir workers and 147 suspected TB patients from hospitals/clinics were obtained. Lesions and sputum samples were cultured for the isolation of Mycobacterium spp. Positive cultures were subjected genus typing, deletion analysis and selected isolates were spoligotyped. Data was analysed using SPSS VERSION 16.0.ResultsPrevalence of 32.5% (52/160) was obtained in cattle. Damboa local government area (LGA), where majority of the infected animals were obtained from had 35.5% bTB prevalence. All categories analysed (breed, age, sex, body conformation and score) had P-values that were not significant (P > 0.05). Sputum culture revealed a prevalence of 3.7% (3/82) from abattoir workers and 12.2% from hospitals/clinics. A significant P-value (0.03) was obtained when positive culture from abattoir and that of hospitals/clinics were compared. Out of the 52 culture positive isolates obtained from cattle, 26 (50%) belonged to M. tuberculosis complex (MTC) and 17/26 (65.4%) were characterized as M. bovis. In humans, 7/12 (58.3%) MTC obtained were characterized as M. tuberculosis. Spoligotyping revealed SB0944 and SB1025 in cattle, while SIT838, SIT61 of LAM10_CAM and SIT1054, SIT46 of Haarlem (H) families were obtained from humans.ConclusionsCattle in Damboa LGA need to be screened for bTB as majority of the infected animals were brought from there. Our findings revealed the presence of SB0944 and SB1025 spoligotypes from cattle in Borno state. We isolated M. tuberculosis strain of the H family mainly domiciled in Europe from humans.

A novel biosensor based on a bio-barcode for the detection of Mycobacterium tuberculosis.

Tuberculosis (TB), the second (after COVID-19) deadliest infectious killer, is a chronic infectious disease caused by infection with Mycobacterium tuberculosis (M.T.), where early diagnosis and management are the key to containing the condition. Here, we report a novel biosensor for the detection of M.T. DNA based on magnetic separation, urease catalysis and silicon nanowire field effect transistor (SiNW FET) detection. M.T. DNA is sequence-specifically captured by magnetic nanoparticles and urease-labelled silica nanoparticles simultaneously to form a sandwich complex and urea is catalyzed into ammonium carbonate by urease modified on a sandwich complex. By using SiNW FET, the detection of M.T. DNA is realized indirectly by the detection of ammonium carbonate. The limit of detection (LOD) was determined to be 78.541 fM. The specificity of the biosensor was confirmed by detecting a panel of bacterial species. The utility of the biosensor was demonstrated in real-sample analysis and the recovery study of M.T. DNA was done in the genomic DNA extracted from cultured Mycobacterium tuberculosis. The biosensor holds promise to become a rapid, sensitive and accurate method for clinical diagnosis.

Maternal and Perinatal Outcomes in Pregnancies Associated with HIV Infection: A Prospective Cohort Study

Introduction: Human Immunodeficiency Virus (HIV) has persisted as the world’s leading infectious killer disease. Globally, around 19.3 million women in the reproductive age group are suffering from HIV, and most of these women are capable of transmitting this infection to their babies. Although pregnancy does not have an adverse effect on the natural history of HIV infection in women, Acquired Immunodeficiency Syndrome (AIDS) has become a leading cause of maternal and perinatal morbidity and mortality in some areas as the epidemic progresses. Aim: To assess the impact of HIV infection on maternal health, the risk of vertical transmission, and neonatal complications. Materials and Methods: This prospective cohort study was conducted at the Department of Obstetrics and Gynaecology, RG Kar Medical College and Hospital, Kolkata, West Bengal, India between March 1, 2021, and August 31, 2022. The study population comprised all pregnant patients with a known positive HIV status or those diagnosed newly during routine antenatal screening at the antenatal Outpatient Department (OPD) and Prevention of Parent to Child Transmission of HIV (PPTCT) clinic, or attending obstetric emergency. After registering in the antenatal clinic, they underwent all routine investigations, including baseline CD4 count, husband’s HIV status, screening for other sexually transmitted diseases, and initiation of Antiretroviral Therapy (ART). Maternal and perinatal outcomes, such as maternal complications, risk of vertical transmission, gestational age at birth, and birth weight of the baby, were assessed throughout the antenatal period and up to six weeks post-delivery. Data were entered into a Microsoft Excel datasheet and analysed using Statistical Packages for Social Sciences (SPSS) version 22.0 software. Categorical data were represented in the form of frequencies and proportions. Chi-square test was used for significance testing, with a p-value <0.05 considered statistically significant. Results: Out of a total of 15,087 deliveries during the study period, 55 were HIV-positive cases, with a prevalence of 0.36%. Both vaginal delivery and cesarean section showed almost similar vertical transmission rates in the newborns, i.e., 4 (14%) and 4 (17%), respectively. Opportunistic infection rates were significantly higher in mothers with lower CD4 counts (<200). Mothers receiving regular ART treatment showed a lower incidence of perinatal complications, such as neonatal sepsis, perinatal asphyxia, convulsions, or perinatal death, i.e., 6 (13.63%), compared to those not on treatment, 8 (72.72%) (p-value=0.005475). Higher rates of vertical transmission were observed in patients with significantly lower Cluster of Differentiation 4 (CD4) counts, 5 (71%) versus 3 (6.8%) (p-value=0.00001). Conclusion: Pregnancy outcomes in terms of maternal risks of infection, risk of vertical transmission, preterm births, foetal deaths, and neonatal complications can be significantly improved by early diagnosis and treatment of HIV infection. Proper antenatal care, early detection, initiation of antiretroviral drugs, and patient compliance with the multidrug regimen are the mainstay of feto-maternal well-being.

Predicting the Number of Reported Pulmonary Tuberculosis in Guiyang, China, Based on Time Series Analysis Techniques.

Tuberculosis (TB) is one of the world's deadliest infectious disease killers today, and despite China's increasing efforts to prevent and control TB, the TB epidemic is still very serious. In the context of the COVID-19 pandemic, if reliable forecasts of TB epidemic trends can be made, they can help policymakers with early warning and contribute to the prevention and control of TB. In this study, we collected monthly reports of pulmonary tuberculosis (PTB) in Guiyang, China, from January 1, 2010 to December 31, 2020, and monthly meteorological data for the same period, and used LASSO regression to screen four meteorological factors that had an influence on the monthly reports of PTB in Guiyang, including sunshine hours, relative humidity, average atmospheric pressure, and annual highest temperature, of which relative humidity (6-month lag) and average atmospheric pressure (7-month lag) have a lagging effect with the number of TB reports in Guiyang. Based on these data, we constructed ARIMA, Holt-Winters (additive and multiplicative), ARIMAX (with meteorological factors), LSTM, and multivariable LSTM (with meteorological factors). We found that the addition of meteorological factors significantly improved the performance of the time series prediction model, which, after comprehensive consideration, included the ARIMAX (1,1,1) (0,1,2)12 model with a lag of 7 months at the average atmospheric pressure, outperforms the other models in terms of both fit (RMSE = 37.570, MAPE = 10.164%, MAE = 28.511) and forecast sensitivity (RMSE = 20.724, MAPE = 6.901%, MAE = 17.306), so the ARIMAX (1,1,1) (0,1,2)12 model with a lag of 7 months can be used as a predictor tool for predicting the number of monthly reports of PTB in Guiyang, China.

Superinfection with SARS-CoV-2 Has Deleterious Effects on Mycobacterium bovis BCG Immunity and Promotes Dissemination of Mycobacterium tuberculosis.

ABSTRACTAn estimated one-third of the world’s population is infected with Mycobacterium tuberculosis, with the majority being vaccinated with Mycobacterium bovis BCG. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a threat, and we must understand how SARS-CoV-2 can modulate both BCG immunity and tuberculosis pathogenesis. Interestingly, neither BCG vaccination nor tuberculosis infection resulted in differences in clinical outcomes associated with SARS-CoV-2 in transgenic mice. Surprisingly, earlier M. tuberculosis infection resulted in lower SARS-CoV-2 viral loads, mediated by the heightened immune microenvironment of the murine lungs, unlike vaccination with BCG, which had no impact. In contrast, M. tuberculosis-infected tissues had increased bacterial loads and decreased histiocytic inflammation in the lungs following SARS-CoV-2 superinfection. SARS-CoV-2 modulated BCG-induced type 17 responses while decreasing type 1 and increasing type 2 cytokines in M. tuberculosis-infected mice. These findings challenge initial findings of BCG’s positive impact on SARS-CoV-2 infection and suggest potential ramifications for M. tuberculosis reactivation upon SARS-CoV-2 superinfection.IMPORTANCE Prior to SARS-CoV-2, M. tuberculosis was the leading infectious disease killer, with an estimated one-third of the world’s population infected and 1.7 million deaths a year. Here, we show that SARS-CoV-2 superinfection caused increased bacterial dissemination in M. tuberculosis-infected mice along with immune and pathological changes. SARS-CoV-2 also impacted the immunity of BCG-vaccinated mice, resulting in decreased interleukin-17 (IL-17) levels, while offering no protective effect against SARS-CoV-2. These results demonstrate that SARS-CoV-2 may have a deleterious effect on the ongoing M. tuberculosis pandemic and potentially limit BCG’s efficacy.

Mycobacterium tuberculosis Transmission in High-Incidence Settings-New Paradigms and Insights.

Tuberculosis has affected humankind for thousands of years, but a deeper understanding of its cause and transmission only arose after Robert Koch discovered Mycobacterium tuberculosis in 1882. Valuable insight has been gained since, but the accumulation of knowledge has been frustratingly slow and incomplete for a pathogen that remains the number one infectious disease killer on the planet. Contrast that to the rapid progress that has been made in our understanding SARS-CoV-2 (the cause of COVID-19) aerobiology and transmission. In this Review, we discuss important historical and contemporary insights into M. tuberculosis transmission. Historical insights describing the principles of aerosol transmission, as well as relevant pathogen, host and environment factors are described. Furthermore, novel insights into asymptomatic and subclinical tuberculosis, and the potential role this may play in population-level transmission is discussed. Progress towards understanding the full spectrum of M. tuberculosis transmission in high-burden settings has been hampered by sub-optimal diagnostic tools, limited basic science exploration and inadequate study designs. We propose that, as a tuberculosis field, we must learn from and capitalize on the novel insights and methods that have been developed to investigate SARS-CoV-2 transmission to limit ongoing tuberculosis transmission, which sustains the global pandemic.