Coinfection of COVID-19 and Tuberculosis in Uganda.

The clinical features and outcomes of tuberculosis (TB) and COVID-19 coinfection are not well established. This short report describes 11 people with TB/COVID-19 coinfection in Uganda. The mean age was 46.9 ± 14.5 years; eight (72.7%) were male and two (18.2%) were coinfected with HIV. All patients presented with cough whose median duration was 71.1 (interquartile range, 33.1, 109) days. Eight (72.7%) had mild COVID-19 whereas two (18.2%) died, including one with advanced HIV disease. All patients were treated with first-line anti-TB drugs and adjunct therapy for COVID-19 using national treatment guidelines. This report presents the possibility of the coexistence of the two diseases and calls for more vigilance, screening, and collective prevention measures for both COVID-19 and TB.

A Review of the Development of Multitarget Molecules against HIV-TB Coinfection Pathogens.

The human immunodeficiency virus (HIV) produces the pathologic basis of acquired immunodeficiency syndrome (AIDS). An increase in the viral load in the body leads to a decline in the number of T lymphocytes, compromising the patient's immune system. Some opportunistic diseases may result, such as tuberculosis (TB), which is the most common in seropositive patients. Long-term treatment is required for HIV-TB coinfection, and cocktails of drugs for both diseases are used concomitantly. The most challenging aspects of treatment are the occurrence of drug interactions, overlapping toxicity, no adherence to treatment and cases of resistance. Recent approaches have involved using molecules that can act synergistically on two or more distinct targets. The development of multitarget molecules could overcome the disadvantages of the therapies used to treat HIV-TB coinfection. This report is the first review on using molecules with activities against HIV and Mycobacterium tuberculosis (MTB) for molecular hybridization and multitarget strategies. Here, we discuss the importance and development of multiple targets as a means of improving adherence to therapy in cases of the coexistence of these pathologies. In this context, several studies on the development of structural entities to treat HIV-TB simultaneously are discussed.

Bayesian spatial modelling of tuberculosis-HIV co-infection in Ethiopia.

An in-depth analysis of the epidemiological patterns of TB/HIV co-infection is essential since it helps to target high-risk areas with effective control measures. The main objective of this study was to assess the spatial clustering of TB/HIV co-infection prevalence in Ethiopia for the year 2018 using district-level aggregated TB and HIV data obtained from the Ethiopian Federal Ministry of Health. The global Moran's index, Getis-Ord [Formula: see text] local statistic, and Bayesian spatial modeling techniques were applied to analyse the data. The result of the study shows that TB among people living with HIV (PLHIV) and HIV among TB patients prevalence were geographically heterogeneous. The highest prevalence of TB among PLHIV in 2018 was reported in the Gambella region (1.44%). The overall prevalence of TB among PLHIV in Ethiopia in the same year was 0.38% while the prevalence of HIV among TB patients was 6.88%. Both district-level prevalences of HIV among TB patients and TB among PLHIV were positively spatially autocorrelated, but the latter was not statistically significant. The local indicators of spatial analysis using the Getis-Ord statistic also identified hot-spots districts for both types of TB/HIV co-infection data. The results of Bayesian spatial logistic regression with spatially structured and unstructured random effects using the Besag, York, and Mollié prior showed that not all the heterogeneities in the prevalence of HIV among TB patients and TB among PLHIV were explained by the spatially structured random effects. This study expanded knowledge about the spatial clustering of TB among PLHIV and HIV among TB patients in Ethiopia at the district level in 2018. The findings provide information to health policymakers in the country to plan geographically targeted and integrated interventions to jointly control TB and HIV.

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.

A tale of three in symbiosis: TB-COVID-19-Bordetella coinfection.

Coinfections/mixed infections are common in the respiratory tract. Many times existing organisms have similar risk factors and clinical features that make the diagnosis difficult. Coronavirus diagnosed in 2019 (COVID-19) and tuberculosis (TB) are two such diseases. Patients with TB have lower cellular immunity and impaired pulmonary function. In such environment, atypical organisms, can infect and make the outcome unfavorable. A 21-year-old malnourished (body mass index- 15 kg/m2) girl presented with fever and cough for 10 days. Sputum for Cartridge Based Nucleic Acid Amplification Test demonstrated Mycobacterium tuberculosis with no rifampin resistance. Fever persisted (100-101°F) and saturation was dropping even after 10 days of antitubercular treatment. A repeat reverse transcription-polymerase chain reaction was done and was positive. In view of persistent symptoms after 20 days, bronchoscopy was done, and cultures showed Bordetella bronchiseptica. Fever and symptoms resolved completely after initiation of the sensitive drug. Diagnostic delay in coinfections can lead to increased morbidity and mortality.

Healthcare seeking patterns for TB symptoms: Findings from the first national TB prevalence survey of South Africa, 2017-2019.

BACKGROUND: Although tuberculosis (TB) symptoms have limited sensitivity they remain an important entry point into the TB care cascade. OBJECTIVES: To investigate self-reported healthcare seeking for TB symptoms in participants in a community-based survey. METHODS: We compared reasons for not seeking care in participants reporting ≥1 of four TB screening symptoms (cough, weight loss, night sweats, fever) in the first South African national TB prevalence survey (2017-2019). We used logistic regression analyses to identify sociodemographic and clinical characteristics associated with healthcare seeking. RESULTS: 5,168/35,191 (14.7%) survey participants reported TB symptoms and 3,442/5168 had not sought healthcare. 2,064/3,442(60.0%) participants intended to seek care, 912 (26.5%) regarded symptoms as benign, 399 (11.6%) reported access barriers(distance and cost), 36 (1.0%) took other medications and 20(0.6%) reported health system barriers. Of the 57/98 symptomatic participants diagnosed with bacteriologically confirmed TB who had not sought care: 38(66.7%) intended to do so, 8(14.0%) regarded symptoms as benign, and 6(10.5%) reported access barriers. Among these 98, those with unknown HIV status(OR 0.16 95% CI 0.03-0.82), p = 0.03 and those who smoked tobacco products(OR 0.39, 95% CI 0.17-0.89, p = 0.03) were significantly less likely to seek care. CONCLUSIONS: People with TB symptoms delayed seeking healthcare, many regarded symptoms as benign while others faced access barriers. Those with unknown HIV status were significantly less likely to seek care. Strengthening community-based TB awareness and screening programmes together with self-screening models could increase awareness of the significance of TB symptoms and contribute to improving healthcare seeking and enable many people with TB to enter the TB care cascade.

Inferior vena cava and renal vein thrombosis: a rare cause of acute kidney injury in tuberculosis.

Recent studies show active tuberculosis induces a prothrombotic state and increases the risk of venous thromboembolism. We report a recently diagnosed case of tuberculosis who presented to our hospital with painful bilateral lower limb swelling and several episodes of vomiting with abdominal pain for 2 weeks. Investigations by a hospital elsewhere 2 weeks ago showed abnormal renal function, misdiagnosed as antitubercular therapy-induced acute kidney injury. D-dimer levels were increased on admission with us, with still deranged renal function. Imaging revealed thrombus at the origin of left renal vein, inferior vena cava and bilateral lower limbs. We started treatment with anticoagulants, which gradually improved kidney function. This case highlights that early diagnosis of renal vein thrombosis and prompt treatment are associated with good clinical outcomes. It also highlights the importance of further studies for risk assessment, prevention strategies and reduction of the burden of venous thromboembolism in patients with tuberculosis.

Tuberculosis and COVID-19 co-infection: description of the global cohort.

BACKGROUND: Information on tuberculosis (TB) and coronavirus disease 2019 (COVID-19) is still limited. The aim of this study was to describe the features of the TB/COVID-19 co-infected individuals from a prospective, anonymised, multicountry register-based cohort with special focus on the determinants of mortality and other outcomes. METHODS: We enrolled all patients of any age with either active TB or previous TB and COVID-19. 172 centres from 34 countries provided individual data on 767 TB-COVID-19 co-infected patients, (>50% population-based). RESULTS: Of 767 patients, 553 (74.0%) out of 747 had TB before COVID-19 (including 234 out of 747 with previous TB), 71 (9.5%) out of 747 had COVID-19 first and 123 (16.5%) out of 747 had both diseases diagnosed within the same week (n=35 (4.6%) on the same day). 85 (11.08%) out of 767 patients died (41 (14.2%) out of 289 in Europe and 44 (9.2%) out of 478 outside Europe; p=0.03): 42 (49.4%) from COVID-19, 31 (36.5%) from COVID-19 and TB, one (1.2%) from TB and 11 from other causes. In the univariate analysis on mortality the following variables reached statistical significance: age, male gender, having more than one comorbidity, diabetes mellitus, cardiovascular disease, chronic respiratory disease, chronic renal disease, presence of key symptoms, invasive ventilation and hospitalisation due to COVID-19. The final multivariable logistic regression model included age, male gender and invasive ventilation as independent contributors to mortality. CONCLUSION: The data suggest that TB and COVID-19 are a "cursed duet" and need immediate attention. TB should be considered a risk factor for severe COVID disease and patients with TB should be prioritised for COVID-19 preventative efforts, including vaccination.

Challenges of diabetes in elderly TB patients.

Diabetes mellitus (DM) and tuberculosis (TB) are worldwide health burdens post-COVID-19. TB is the second-leading cause of death by a single infectious microbe. There is much evidence around the world about the responsibility of TB-DM co-morbidity. Both TB and DM prevalence is high in low- and middle-income countries. Especially the elderly with diabetes are more prone to TB infection due to compromised immune systems. Diabetic patients are three times as likely to develop tuberculosis as non-diabetic patients. DM interferes with the status of TB and leads to undesirable outcomes in the treatment of TB. This may later lead to the development of multidrug-resistant tuberculosis (MDR-TB). The coexistence of TB and DM leads to a high mortality rate and therefore becomes an enormous challenge for the medical field. This viewpoint includes the most current information about TB and DM, disease complications, treatment strategies, challenges to be faced in disease management and the importance of TB-DM bidirectional screening in older adults, which helps in early detection and better treatment programme.

A health systems intervention to strengthen the integration of tuberculosis and COVID-19 detection: Outcomes of a quasi-experimental study in a high burden tuberculosis district in KwaZulu Natal, South Africa.

OBJECTIVES: The adverse effects of the COVID-19 pandemic on tuberculosis (TB) detection have been well documented. Despite shared symptoms, guidance for integrated screening for TBand COVID-19 are limited, and opportunities for health systems strengthening curtailed by lockdowns. We partnered with a high TB burden district in KwaZulu-Natal, South Africa, to co-develop an integrated approach to assessing COVID-19 and TB, delivered using online learning and quality improvement, and evaluated its performance on TB testing and detection. METHODS: We conducted a mixed methods study incorporating a quasi-experimental design and process evaluation in 10 intervention and 18 control clinics. Nurses in all 28 clinics were all provided access to a four-session online course to integrate TB and COVID-19 screening and testing, which was augmented with some webinar and in-person support at the 10 intervention clinics. We estimated the effects of exposure to this additional support using interrupted time series Poisson regression mixed models. Process evaluation data comprised interviews before and after the intervention. Thematic coding was employed to provide explanations for effects of the intervention. RESULTS: Clinic-level support at intervention clinics was associated with a markedly higher uptake (177 nurses from 10 intervention clinics vs. 19 from 18 control clinics). Lack of familiarity with online learning, and a preference for group learning hindered the transition from face-to-face to online learning. Even so, any exposure to training was initially associated with higher rates of GeneXpert testing (adjusted incidence ratio [IRR] 1.11, 95% confidence interval 1.07-1.15) and higher positive TB diagnosis (IRR 1.38, 1.11-1.71). CONCLUSIONS: These results add to the knowledge base regarding the effectiveness of interventions to strengthen TB case detection during the COVID-19 pandemic. The findings support the feasibility of a shift to online learning approaches in low-resource settings with appropriate support and suggest that even low-intensity interventions are capable of activating nurses to integrate existing disease control priorities during pandemic conditions.

Effects of tuberculosis and/or HIV-1 infection on COVID-19 presentation and immune response in Africa.

Few studies from Africa have described the clinical impact of co-infections on SARS-CoV-2 infection. Here, we investigate the presentation and outcome of SARS-CoV-2 infection in an African setting of high HIV-1 and tuberculosis prevalence by an observational case cohort of SARS-CoV-2 patients. A comparator group of non SARS-CoV-2 participants is included. The study includes 104 adults with SARS-CoV-2 infection of whom 29.8% are HIV-1 co-infected. Two or more co-morbidities are present in 57.7% of participants, including HIV-1 (30%) and active tuberculosis (14%). Amongst patients dually infected by tuberculosis and SARS-CoV-2, clinical features can be typical of either SARS-CoV-2 or tuberculosis: lymphopenia is exacerbated, and some markers of inflammation (D-dimer and ferritin) are further elevated (p < 0.05). Amongst HIV-1 co-infected participants those with low CD4 percentage strata exhibit reduced total, but not neutralising, anti-SARS-CoV-2 antibodies. SARS-CoV-2 specific CD8 T cell responses are present in 35.8% participants overall but undetectable in combined HIV-1 and tuberculosis. Death occurred in 30/104 (29%) of all COVID-19 patients and in 6/15 (40%) of patients with coincident SARS-CoV-2 and tuberculosis. This shows that in a high incidence setting, tuberculosis is a common co-morbidity in patients admitted to hospital with COVID-19. The immune response to SARS-CoV-2 is adversely affected by co-existent HIV-1 and tuberculosis.

Incidence and Risk of Lung Cancer in Tuberculosis Patients, and Vice Versa: A Literature Review of the Last Decade.

Background: The incidence and risk of both lung cancer (LC) and tuberculosis (TB) are increasing rapidly. These two diseases frequently exist together and can influence the incidence and risk of each other. The aim of the current review was to summarize the incidence and risk of LC in TB patients, and vice versa, short out research gap, and contemplate future research perspectives. Methodology. PubMed and Scopus databases, and Google Scholar search engine were searched for epidemiological studies that investigated the incidence and risk of TB and LC, published since January 2011 to April 2022, and written in English. We used the searching keyword "tuberculosis" combined with "lung cancer" and associated medical subject heading (MeSH) to retrieve eligible research articles. We retrieved information's regarding the diagnosis of TB and LC, confounders, the associations of TB and LC, and incidence and risks of each other. Results: We found higher incidence rate and risks (1.64 to 6 times higher) of LC in TB patients in comparison to non-TB participants. However, the incidence rate and risks of TB in LC patients were comparatively low. Male patients were exhibited higher risks than female. The medical comorbidities, smoking habits, and age can also influence the associations and risks of LC in TB patients or vice versa. Conclusion: Our summarized studies might suggest that existing active TB may increase the incidence and risk of LC. However, large prospective cohort study is warranted to explore the real scenario worldwide.

Prevalence of covid-19 among patients with chronic obstructive pulmonary disease and tuberculosis.

BACKGROUND: The exhaustive information about non-communicable diseases associated with COVID-19 and severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) are getting easier to find in the literature. However, there is a lack of knowledge regarding tuberculosis (TB) and chronic obstructed pulmonary disease (COPD), with numerous infections in COVID-19 patients. OBJECTIVES: Priority is placed on determining the patient's prognosis based on the presence or absence of TB and COPD. Additionally, a comparison is made between the risk of death and the likelihood of recovery in terms of time in COVID-19 patients who have either COPD or TB. METHODOLOGY: At the DHQ Hospital in Muzaffargarh, Punjab, Pakistan, 498 COVID-19 patients with TB and COPD were studied retrospectively. The duration of study started in February 2022 and concluded in August 2022. The Kaplan-Meier curves described time-to-death and time-to-recovery stratified by TB and COPD status. The Wilcoxon test compared the survival rates of people with TB and COPD in two matched paired groups and their status differences with their standard of living. RESULTS: The risk of death in COVID-19 patients with TB was 1.476 times higher than in those without (95% CI: 0.949-2.295). The recovery risk in COVID-19 patients with TB was 0.677 times lower than in those without (95% CI: 0.436-1.054). Similarly, patients with TB had a significantly shorter time to death (p=.001) and longer time to recovery (p=.001). CONCLUSIONS: According to the findings, the most significant contributor to an increased risk of morbidity and mortality in TB and COPD patients was the COVID-19.KEY MESSAGESSARS-Cov-19 is a new challenge for the universe in terms of prevention and treatment for people with tuberculosis and chronic obstructive pulmonary disease, among other diseases.Propensity score matching to control for potential biases.Compared to hospitalized patients with and without (TB and COPD) had an equivalently higher mortality rate.

Effect of HIV status and antiretroviral treatment on treatment outcomes of tuberculosis patients in a rural primary healthcare clinic in South Africa.

BACKGROUND: Tuberculosis (TB) remains the leading cause of death among human immunodeficiency virus (HIV) infected individuals in South Africa. Despite the implementation of HIV/TB integration services at primary healthcare facility level, the effect of HIV on TB treatment outcomes has not been well investigated. To provide evidence base for TB treatment outcome improvement to meet End TB Strategy goal, we assessed the effect of HIV status on treatment outcomes of TB patients at a rural clinic in the Ugu Health District, South Africa. METHODS: We reviewed medical records involving a cohort of 508 TB patients registered for treatment between 1 January 2013 and 31 December 2015 at rural public sector clinic in KwaZulu-Natal province, South Africa. Data were extracted from National TB Programme clinic cards and the TB case registers routinely maintained at study sites. The effect of HIV status on TB treatment outcomes was determined by using multinomial logistic regression. Estimates used were relative risk ratio (RRR) at 95% confidence intervals (95%CI). RESULTS: A total of 506 patients were included in the analysis. Majority of the patients (88%) were new TB cases, 70% had pulmonary TB and 59% were co-infected with HIV. Most of HIV positive patients were on antiretroviral therapy (ART) (90% (n = 268)). About 82% had successful treatment outcome (cured 39.1% (n = 198) and completed treatment (42.9% (n = 217)), 7% (n = 39) died 0.6% (n = 3) failed treatment, 3.9% (n = 20) defaulted treatment and the rest (6.6% (n = 33)) were transferred out of the facility. Furthermore, HIV positive patients had a higher mortality rate (9.67%) than HIV negative patients (2.91%)". Using completed treatment as reference, HIV positive patients not on ART relative to negative patients were more likely to have unsuccessful outcomes [RRR, 5.41; 95%CI, 2.11-13.86]. CONCLUSIONS: When compared between HIV status, HIV positive TB patients were more likely to have unsuccessful treatment outcome in rural primary care. Antiretroviral treatment seems to have had no effect on the likelihood of TB treatment success in rural primary care. The TB mortality rate in HIV positive patients, on the other hand, was higher than in HIV negative patients emphasizing the need for enhanced integrated management of HIV/TB in rural South Africa through active screening of TB among HIV positive individuals and early access to ART among HIV positive TB cases.

Paracentral acute middle maculopathy with occlusive retinal vasculitis in presumed intraocular tuberculosis and hyperhomocysteinemia.

A male patient presented with a sudden visual decline in the right eye (OD). Fundus revealed bilateral vasculitis; OD also showed an occluded inferior retinal vein and a wedge-shaped retinal opacification of the inferior macula and nasal retina. Fluorescein angiography revealed occlusive retinal vasculitis, while optical coherence tomography showed paracentral acute middle maculopathy (PAMM) in the OD. A thorough systemic evaluation revealed hyperhomocysteinemia and a positive Mantoux test. A diagnosis of PAMM with occlusive retinal vasculitis in presumed intraocular tuberculosis and hyperhomocysteinemia was made. Retinal vasculitis improved with oral corticosteroid, intravitreal anti-vascular endothelial growth factor and laser photocoagulation. However, the patient declined antitubercular therapy despite recommendations. This unique report indicates that PAMM may complicate tubercular retinal vasculitis, especially in the presence of systemic hypercoagulable states.

[Clinical Properties of COVID-19 Developed in the Patients with Tuberculosis]. / Tüberküloz Hastalarinda Gelisen COVID-19'un Klinik Özellikleri.

There are limited publications about the Coronavirus disease 19 (COVID-19) clinic developing in the patients with active tuberculosis (TB). In this study, it was aimed to determine some clinical features of patients diagnosed with TB who also had COVID-19. In this retrospective cross-sectional study, 71 patients with COVID-19 were evaluated out of a total of 595 patients diagnosed with TB in our province between 2015 and 2021. After contracting COVID-19, a total of nine (12.6%) TB patients were hospitalized, five (7%) patients were admitted to the intensive care unit, three (4.2%) were intubated, and one (1.4%) died due to severe COVID-19. The frequency of such health problems was found to be higher than the normal population living in the same province. None of these complications were observed in a total of 40 female TB patients, and the hospital and intensive care unit admission rates for men were significantly higher than for women. The results of this study showed that men with active TB had more health problems due to COVID-19 than the normal population. Comprehensive studies are needed to detail the resilience of female TB patients against COVID-19.

Identification of Prognostic Metabolomic Biomarkers at the Interface of Mortality and Morbidity in Pre-Existing TB Cases Infected With SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection currently remains one of the biggest global challenges that can lead to acute respiratory distress syndrome (CARDS) in severe cases. In line with this, prior pulmonary tuberculosis (TB) is a risk factor for long-term respiratory impairment. Post-TB lung dysfunction often goes unrecognized, despite its relatively high prevalence and its association with reduced quality of life. In this study, we used a metabolomics analysis to identify potential biomarkers that aid in the prognosis of COVID-19 morbidity and mortality in post-TB infected patients. This analysis involved blood samples from 155 SARS-CoV-2 infected adults, of which 23 had a previous diagnosis of TB (post-TB), while 132 did not have a prior or current TB infection. Our analysis indicated that the vast majority (~92%) of post-TB individuals showed severe SARS-CoV-2 infection, required intensive oxygen support with a significantly high mortality rate (52.2%). Amongst individuals with severe COVID-19 symptoms, we report a significant decline in the levels of amino acids, notably the branched chains amino acids (BCAAs), more so in the post-TB cohort (FDR <= 0.05) in comparison to mild and asymptomatic cases. Indeed, we identified betaine and BCAAs as potential prognostic metabolic biomarkers of severity and mortality, respectively, in COVID-19 patients who have been exposed to TB. Moreover, we identified serum alanine as an important metabolite at the interface of severity and mortality. Hence, our data associated COVID-19 mortality and morbidity with a long-term metabolically driven consequence of TB infection. In summary, our study provides evidence for a higher mortality rate among COVID-19 infection patients who have history of prior TB infection diagnosis, which mandates validation in larger population cohorts.