Stridor in Tuberculosis and COVID-19 Coinfection

Introduction: Tuberculosis (TB) is a communicable disease with active and latent phases. In the United States, up to 13 million people have latent infections with 5-10% of individuals developing active infection. Testing is imperative to identify such cases. Case: A 71-year-old woman with squamous cell carcinoma of the lung status post chemotherapy and radiation and sarcoidosis on chronic steroids was admitted for evaluation of a several month history of progressive hoarseness and supraglottic edema. Prior vocal cord biopsies showed ulcerated keratosis with granulomatous inflammation and reactive atypica. GMS stains were negative, and there was no evidence of malignancy. Repeat laryngoscopy showed scattered white lesions throughout the larynx and an enlarged epiglottis. Due to suspicion for laryngeal candidiasis, Fluconazole was started. CT chest showed bilateral lung nodules and right upper lobe airspace disease thought to represent post-treatment changes. On day four of admission, the patient experienced several episodes of hemoptysis. Sputum culture grew Staphylococcus aureus, and patient was started on Vancomycin. The next day, the patient experienced recurrent hemoptysis and subsequent PEA arrest. Multiple rounds of ACLS were unsuccessful, and the patient died. Autopsy showed Mycobacteria tuberculosis PCR positivity from the right upper lobe, necrotic pulmonary nodules with necrotizing granulomas with acid-fast bacilli, acid fast bacilli involving the epiglottis and larynx, diffuse pulmonary hemorrhage, and sarcoidosis with non-necrotizing granulomas involving lymph nodes, small bowel, spleen, liver, and bone marrow. Discussion: The presence of hoarseness, airway edema, and lung nodules in a patient with a history of malignancy and sarcoidosis on immunosuppressive therapy presented a complex diagnostic challenge. Concomitant sarcoidosis and tuberculosis is extremely rare, and TB was suspected to be a complication of prolonged steroid use in this patient. Laryngeal tuberculosis accounts for less than one percent of all tuberculosis cases, and patients can present with dysphonia, dysphagia or cough due to involvement of the vocal cords. Given the association between laryngeal tuberculosis and pulmonary involvement, evaluation for pulmonary tuberculosis is crucial. Patients with laryngeal and pulmonary tuberculosis are at increased risk of severe, potentially life-threatening airway compromise due to involvement of both upper and lower airways. Multidisciplinary collaboration with Otolaryngology and Infectious Diseases is essential for accurate diagnosis and management to prevent patient morbidity and mortality, as well as transmission of infection.

The COVID-19 pandemic affected millions of people worldwide, becoming a challenge of every nation. Since the COVID-19 can present wide spectrum of clinical signs and symptoms, patients with symptoms similar to that of COVID-19 may be misdiagnosed during the context of COVID-19 pandemic. In this regard, various co-infections may affect the outcome of COVID-19 patients if it lefts undiagnosed, especially during the administration of immunosuppressive drugs. Similar to COVID-19, TB affect the lungs and respiratory airways primarily. These two diseases have resembling symptoms, including dry cough, fever, and dyspnea. Due to the importance of early COVID-19 diagnosis, many other respiratory infectious diseases such as tuberculosis (TB) may be missed. Herein, a case of COVID-19 and tuberculosis co-infection is presented.

Extrapulmonary tuberculosis (EPTB) accounts for less than 6% of all tuberculosis (TB) cases in Poland, although in other countries (European in particular) this proportion is much higher. The study was undertaken to evaluate the clinical and epidemiological differences in patients hospitalized in one of Otolaryngology Departments in Poland during 36 years. In a retrospective study, 71 patients were identified and divided into three groups according to the study period: I - 1978-1989 (30 patients, 42%), II - 1990-2001 (19 patients, 27%) and III - 2002-2013 (22 patients, 31% of all cases). In each case histological examination of biopsy specimens was available. Larynx TB (54.9%) was most common, followed by cervical lymph nodes TB (29.6%) and auris TB (8.5%). In laryngeal TB, glottic region was most often affected (76.9%). Patients with larynx TB were mainly men (87.2%), 10 years older than women in each study period. However, in lymph nodes TB group, women constituted 66.7% of cases and were twice as old as men (64.0 vs. 34.7 yrs). Bacteriological confirmation was made in only one patient. The number of patients diagnosed in our center declined in the first period of 12 years and remained stable over the last 24 years, as were the common sites of head and neck EPTB (larynx and cervical lymph nodes). In patients with head and neck TB the biopsy specimens should be examined not only histologically but also for the presence of Mycobacterium tuberculosis.

IntroductionCOVID-19 and tuberculosis (TB) represent global threats to the public health system. The impact of COVID-19 on TB results in a reduction in the number of notified TB cases, delayed diagnosis and treatment, and increased case fatality and mortality rates. The aim of the study was to analyze the TB/COVID-19 co-infected cohort in Serbia as a low-burden country and compare it to the global TB/COVID-19 cohort.MethodsA retrospective analysis was done on 53 TB and COVID-19 co-infected patients treated in COVID hospital “Batajnica” in Belgrade and Special Hospital for Pulmonary Diseases “Ozren” Sokobanja in the period from 6 March 2020 to 1 April 2022. A comparative analysis with the global cohort published recently was also performed.ResultsTB/COVID-19 cohort in Serbia included significantly fewer migrants and diabetes cases, but more cases with chronic respiratory diseases compared to the global. Descriptive analysis of TB cases in the Serbian TB/COVID-19 cohort showed fewer cases diagnosed with sputum smear and Gene Xpert/HAIN, fewer EPTB and mono-resistant cases, and more cases diagnosed with solid culture, unilateral pulmonary infiltrate (with bilateral cavity lesions), and bilateral pulmonary infiltrate (no cavities) compared to TB/COVID-19 cases worldwide. Nasal congestion and fever were more common COVID-19 symptoms in the global cohort. Radiology was more commonly used for the diagnosis of COVID-19 in Serbia. Typical bilateral ground opacities were less common among Serbian patients. Serbian patients spent fewer days in the hospital and achieved a higher PCR conversion rate and TB treatment success rate.ConclusionThe Serbian TB/COVID-19 cohort achieved a higher treatment success rate compared to the global cohort. Encouraging vaccination against SARS-CoV-2 for people with a current or past TB disease, as well as rapid diagnosis and targeted treatment of TB in highly specialized pulmonology institutions, presents key points to avoid excessive morbidity and mortality.

Co-infection with COVID-19 and tuberculosis (TB) often leads to symptoms such as fever, coughing, low blood pressure, altered blood cell counts, elevated liver enzyme levels, and reduced hemoglobin. Additionally, there is significant concern regarding lung damage caused by severe COVID-19, which increases susceptibility to TB. On May 19, 2022, a 50-year-old retired Black African woman visited the emergency department with a sore throat, a 12 kg weight loss over the previous month, and shortness of breath that began a day earlier. She also experienced muscle weakness, fever, a productive cough, loss of appetite, headache, and 3 days of night sweats. Chest auscultation revealed reduced breath sounds in the right upper and middle lung regions. A throat swab polymerase chain reaction (PCR) test confirmed a COVID-19 diagnosis 36 hours later. During her hospital stay, the patient required continuous oxygen therapy via a nasal cannula at 4 L per minute for the first 5 days. She remained on anti-tubercular medication and received intravenous ceftriaxone at a dosage of 1 g daily for 5 days to prevent hospital-acquired infections. Patients with active pulmonary tuberculosis (TB) have a poorer prognosis and are at risk of developing COVID-19. Both TB and COVID-19 are infectious diseases that primarily target the lungs. Mortality rates associated with COVID-19 are notably higher in individuals with active pulmonary TB. COVID-19 and Mycobacterium tuberculosis are among the most critical global health challenges. TB infection is linked to a heightened risk of severe COVID-19 outcomes.

To study the clinicopathologic features, histologic diagnosis and differential diagnosis of primary mucosal tuberculosis (TB) in the head and neck region. Forty-seven cases of primary mucosal TB of the head and neck region were studied by hematoxylin-eosin and Ziehl-Neelsen stains. The clinical and pathologic features were analyzed with review of the literature. The patients included 26 male and 21 female, with mean age 47.1 years (range 14-84 years). There were three sinonasal TB, 19 nasopharyngeal TB, two oropharyngeal TB, 18 laryngeal TB, four middle ear TB, one salivary gland TB and one laryngeal TB complicating laryngeal cancer. The initial symptoms were nasal obstruction, mucopurulent rhinorrhea, epistaxis, snoring, hoarseness, dysphagia, odynophagia, serous otitis, hearing loss, tinnitus, and otalgia. Physical examination result was variable, from an apparently normal mucosa, to an evident mass, or a mucosa with an adenotic or swollen appearance, ulcers, leukoplakic areas, and various combinations thereof. CT and MRI findings included diffuse thickening, a soft-tissue mass, calcification within the mass and bone destruction resembling malignancy. Histologic examination showed granulomas with a central necrotic focus surrounded by epithelioid histiocytes and multinucleated Langhan's giant cells. Acid-fast bacilli were difficult to demonstrate but found in 13/45 cases. Follow-up data were available in 42 patients. Primary TB arising in the head and neck mucosa is rare. It may mimic or co-exist with other conditions. The characteristic histopathology is a granuloma with central caseous necrosis and Langhans'giant cells. Identification of acid-fast bacilli and bacteriologic culture confirm the diagnosis of mycobacterial disease.

BackgroundDespite incarcerated population being at an increased risk of tuberculosis (TB) and serving as a potential source of TB transmission for the general population, prison TB remains understudied. Given its adverse impact on progress towards TB elimination, World Health Organization (WHO) has identified prison TB research as a top priority to guide TB treatment/control interventions.MethodsWe retrospectively analyzed 921 notified TB cases that were diagnosed at Kality Federal Prison, Ethiopia during 2009–2017. To assess trends of microbiologically confirmed pulmonary TB (PTB), extra-pulmonary TB (EPTB), and TB-HIV co-infection, an ecological analysis of aggregated cases was used to report trends over time. Additionally, we used multivariable log binomial regression to identify patient characteristics associated with microbiologically confirmed PTB, EPTB, and TB-HIV co-infection.ResultsMicrobiologically confirmed PTB proportion increased over time. Young age was identified as an important risk factor for EPTB (adjusted prevalence ratio [aPR] = 1.74, 95% CI 0.97, 3.13) while HIV coinfection was negatively associated with EPTB (aPR = 0.73, 95% CI 0.55, 0.97). While previous TB history was associated with a lower likelihood of EPTB (aPR = 0.42, 95% CI 0.25, 0.70), it was associated with an increased risk of TB-HIV coinfection (aPR = 1.37, 95% CI 1.10, 1.71). Clinically diagnosed PTB patients were more likely to have TB-HIV coinfection compared to microbiologically confirmed PTB patients (aPR = 1.32, 95% CI 1.02, 1.72).ConclusionsIncreasing proportion of microbiologically confirmed PTB may suggest delayed access to treatment, severe disease and increased risk of intramural transmission. Associations with clinical/demographic factors varied for different types of TB and were not always consistent with what has been previously reported for the general population, necessitating the need to refocus prison TB control/treatment strategies based on context specific epidemiological factors.

AB0387 Incidence and Risk Factors for Tuberculosis in Japanese Patients with Rheumatoid Arthritis During a 12-Year Observational Period Using the Iorra Cohort

Aim. To study the features of clinical and radiological manifestations and diagnosis of COVID-19, respiratory tuberculosis and opportunistic lung infections (OIL) coinfection in patients with late stages of HIV-infection with immunodeficiency.
 Materials and methods. The study included 29 patients with COVID-19 coinfection, respiratory tuberculosis and opportunistic lung infections in the late stages of HIV-infection with immunodeficiency (group 1) and 29 patients similar in all parameters without COVID-19 (group 2). All patients were underwent clinical and laboratory, radiation and bronchological examination, and microbiological, immunological, molecular genetic, cytological and histological examination of diagnostic material of the respiratory tract, cerebrospinal and pleural fluid, blood, urine and feces to identify pathogens of coinfection. Statistical data processing was carried out using the Microsoft Office Excel 2010 program with the calculation of the average in the group and the standard error of the average, confidence interval.
 Results. It has been established that co-infection with COVID-19, respiratory tuberculosis and opportunistic lung infections in patients with late stages of HIV-infection with immunodeficiency is manifested by a pronounced intoxication syndrome, bronchopulmonary manifestations and symptoms of damage to other organs and systems, which is due to the generalization of tuberculosis with extrapulmonary lesions and the development of opportunistic lung infections, as in patients without COVID-19. A computed tomogram of the chest organs with this coinfection visualizes the syndrome of dissemination, the syndrome of adenopathy and the syndrome of pathology of the pulmonary pattern, represented by the compaction of interstitial tissue in the frosted glass type, which is associated with the simultaneous layering of various pathologies, which complicates their differential diagnosis. This determines the similarity of clinical and radiological manifestations of COVID-19 coinfection, respiratory tuberculosis and opportunistic lung infections in patients with late-stage HIV-infection with immunodeficiency, as in patients without COVID-19. This requires complex microbiological and molecular genetic research methods to identify specific pathogens for the appointment of timely treatment.
 Conclusion. Patients with COVID-19 coinfection, respiratory tuberculosis and opportunistic lung infections in the late stages of HIV-infection with immunodeficiency pose a high risk of infection in a healthy population, taking into account their social maladaptation and non-adherence to examination and treatment. This requires an active diagnosis of COVID-19 in all patients with respiratory tuberculosis and HIV-infection who are registered in the office of anti-tuberculosis care for HIV-infected in an anti-tuberculosis dispensary, for emergency isolation and treatment.

Two patients with laryngeal tuberculosis in the absence of extensive pulmonary tuberculosis are presented. In both, tuberculin testing of household members failed to show infectiousness of their disease. This contradicts the commonly held view that laryngeal tuberculosis is invariably highly infectious. The extent and activity of pulmonary disease probably determines the infectiousness of patients with laryngeal tuberculosis rather than the laryngeal lesion per se.

HTLV-1 modifies the immune response and clinical presentation of bacterial, fungal and helminthic infections. There are also evidences that helminthic infections may modify disease expression related to HTLV-1, increasing the occurrence of Adult T cell leukemia (ATL) and decreasing the development of HTLV-1 associated myelopathy or tropical spastic paraparesis (HAM/TSP). Recently it has been shown that HTLV-1 increases susceptibility for tuberculosis (TB) but the consequences of this co-infection in the clinical course of TB and HTLV-1 infection is not so clear. The aim of this study was to evaluate if TB influences neurologic disease in HTLV-1 infected subjects and to evaluate sequels of TB in HTLV-1 infected individuals. This is a nested case control study with the participation of 32 patients with previous diagnosis of TB and positivity sorology for HTLV-1 and 32 controls with HTLV-1 without TB paired by age, gender and time of admission in the clinic. Of the 32 patients with TB 29 had pulmonary TB, one had pleural TB, one laryngeal TB and the other lymphonode TB. Only 2 (6,2%) developed a second episode of TB. Among those who have been treated for TB 8 (25%) patients complained of dyspnea, 3 without evidence of pulmonary disease, 3 cases had chronic obstructive pulmonary disease (COPD) and two cases had bronchial overactivity. Regarding HTLV-1 associated disease probable HAM/TSP was diagnosed in 4 (12,5%) of the TB patients and in 6 (18,7%) of the patients who only have HTLV-1 infection (P > 0.05). Definitive HAM/TSP was diagnosed in 10 (31,2%) of the co-infected patients with HTLV-1 and TB and in 4 (12,5%) in the group who only had HTLV-1 (P < 0.05). While HTLV-1 appears to not influence the severity of Micobacterium tuberculosis infection TB was highly associated with HAM/TSP.

Tuberculosis (TB) is responsible for a substantial public health burden worldwide, with a heterogeneous geographical distribution. Sub-Saharan Africa accounts for almost one-quarter of the global burden of TB. This is associated with high HIV-prevalence, low socio-demographic development, and poor living and working conditions. Identification of high-risk populations and locations within countries with a high burden of TB has the potential to improve the cost-effectiveness of TB control strategies.Two groups of 30 countries account for almost 90 per cent of the global burden of TB disease and TB and HIV co-infection. Ethiopia is in both groups, with both high-TB and TB and HIV co-infection. However, information is limited to the geographical distribution of high-risk areas which could inform targeted intervention. The overall aim of the researches in this Thesis is to enhance the TB control program in Ethiopia by providing more detailed knowledge of the distribution of TB, and the contributory role of HIV, low sociodemographic development and poor living and working conditions. This will provide sustained TB control in Ethiopia and enable enhanced strategic implementation of the “End TB strategy.”The first part (Chapters 1-3) of this Thesis highlights the available evidence on the geographical variation of TB and the burden of TB and HIV co-infection. Chapter 4 presents a systematic review of published studies on the effects of altitude and temperature on TB notification. This review indicated that studies examining the correlations between altitude and temperature on TB notification are limited in number. Despite low study power, the report demonstrated that living in low-altitude and high-temperature settings may increase TB risk.Chapter 5 presents evidence from a systematic review and meta-analysis conducted to estimate the prevalence of HIV in patients diagnosed with TB in sub-Saharan Africa. The prevalence of HIV in diagnosed TB patients (HIV/TB) showed substantial heterogeneity with an overall prevalence estimate of HIV/TB of 31.8 per cent. Heterogeneity in HIV/TB between studies was mainly attributable to geographic region and HIV prevalence. The Eastern and Southern sub-Saharan African region had a higher prevalence of HIV/TB (34.4 per cent) compared to Western and Central sub-Saharan Africa (27.3 per cent). However, the prevalence decreased more in the Eastern and Southern sub-Saharan African region than Western and Central sub-Saharan African between 2000 and 2010. This study suggests that collaborative TB and HIV activities need to be strengthened and sustained to achieve an end to the TB epidemic.Based on evidence from previous chapters, Chapters 6 and 7 present the spatial distributions of TB and HIV, profiling the sociodemographic and environmental determinants in the Amhara region of Ethiopia, using separate TB and HIV cluster detection methods. These studies demonstrated the spatial heterogeneity of both diseases. Both district-level TB notifications, reported between 2014 and 2017, and HIV infection rates, between 2015 and 2017, were spatially clustered in the border areas of the Amhara region of Ethiopia. Regression analyses demonstrated that the most important factor associated with both TB and HIV clustering was the proportion of seasonal migrant populations in the district. Additional factors associated with high notifications of TB were the proportion of people living in urban areas, crowding, the percentage of males, people living with HIV (PLHIV) /1000 population, access to health care, and the use of charcoal for cooking. Living at low altitude was also associated with TB clustering, which was consistent with the review findings in Chapter 4. Low educational status was also associated with HIV high-risk areas.Chapter 8 presents the epidemiology of TB and HIV co-infection in Ethiopia. This chapter elucidates the progress of the implementation of collaborative TB and HIV activities and the consequent impact on the national TB control program. Findings from sentinel surveillance of TB and HIV co-infection data, from 76 health facilities in Ethiopia, suggest that collaborative TB and HIV services were either not uniform or not consistently implemented between 2010 and 2015. However, encouragingly, intensified TB case finding in PLHIV and the screening of HIV patients for TB diagnosis increased. This Thesis provides more detailed evidence on the distribution of TB and associated HIV infection in Ethiopia, using geo-spatial tools and modelling. It shows that TB and HIV infection are geographically heterogeneous and co-clustered in the Northwest border areas of Ethiopia, likely influenced by the proportion of seasonal migrants in common. This information provides the basis to enhance the strategic implementation of TB control program in Ethiopia. It also highlights the need to strengthen integrated TB and HIV management, to address social determinants of TB, and to deal with issues of population movement to control and prevent HIV and TB in Ethiopia, and thus achieve the “End-TB” goal.

Paediatric Tuberculosis in a Teaching Hospital: A 5 Year Review

To investigate whether an unrecognised diagnosis of tuberculosis (TB) at the start of antiretroviral therapy (ART) influences subsequent CD4+ T cell (CD4) count recovery in an urban HIV clinic in Uganda. In a retrospective cohort study, a multivariable polynomial mixed effects model was used to estimate CD4 recovery in the first 96 weeks of ART in two groups of patients: prevalent TB (started ART while on TB treatment), unrecognised TB (developed TB within 6 months after start ART). Included were 511 patients with a median baseline CD4 count of 57 cells/mm(3) (interquartile range: 22-130), of whom 368 (72%) had prevalent TB and 143 (28%) had unrecognised TB. Compared with prevalent TB, unrecognised TB was associated with lower CD4 count recovery at 96 weeks: -22.3 cells/mm(3) (95% confidence interval -43.2 to -1.5, P = 0.036). These estimates were adjusted for gender, age, baseline CD4 count and the use of zidovudine-based regimen. Unrecognised TB at the time of ART initiation resulted in impaired CD4 recovery compared with TB treated before ART initiation. More vigilant screening with more sensitive and rapid TB diagnostics prior to ART initiation is needed to decrease the risk of ART-associated TB and sub-optimal immune reconstitution.

The larynx is the second most commonly affected site in the head and neck region in patients with extrapulmonary tuberculosis (TB). Despite this, the prevalence of laryngeal TB is largely unknown, particularly in areas with a high TB burden. The laboratory diagnosis of TB includes microscopy, culture and molecular testing. The aims of this study were to determine the prevalence of laryngeal TB in patients presenting with laryngeal pathology in a region with a high TB burden and to determine the optimal diagnostic methods for the diagnosis of laryngeal TB. This was a prospective descriptive study of 80 adult patients undergoing direct laryngoscopy and biopsy for laryngeal pathology in the Department of Otorhinolaryngology, Universitas Academic Hospital, Bloemfontein, South Africa over a 1year period. Histopathological and microbiological investigations (microscopy, Xpert MTB/RIF, and TB culture) were performed on all laryngeal biopsies. Five (6.25%) out of 80 patients were diagnosed with laryngeal TB. In one patient, the Xpert MTB/RIF assay was positive on the laryngeal tissue and histology showed granulomas. Two patients had granulomas on histology although the microbiological tests on the tissue were negative. Two patients had only positive tissue cultures for Mycobacterium tuberculosis. None of the biopsies had positive Ziehl-Neelsen stains. The results suggest that the diagnosis of laryngeal TB required a combination of histopathology, culture and PCR and that the Xpert MTB/RIF assay is not a sensitive test for the diagnosis of laryngeal TB.