Diagnosis and management of severe pulmonary and extrapulmonary tuberculosis in critically ill patients:A mini review for clinicians

Among critically ill patients,severe pulmonary and extrapulmonary tuberculosis has high morbidity and mortality.Yet,it is a diagnostic challenge given its nonspecific clinical symptoms and signs in early stages of the disease.In addition,management of severe pulmonary and extrapulmonary tuberculosis is complicated given the high risk of drug-drug interactions,drug-disease interactions,and adverse drug reactions.To help clinicians acquire an up-to-date approach to severe tuberculosis,this paper will provide a narrative review of contemporary diagnosis and management of severe pulmonary and extrapulmonary tuberculosis in critically ill patients.

Primary extrapulmonary tuberculosis diagnosis warrants extraprecautious pulmonary tuberculosis exclusion workup

This editorial article takes an opportunity to apprehend the diagnostic challenges of primary gastrointestinal tuberculosis(an uncommon extrapulmonary tuberculosis condition)utilizing the recently published case report of a young male with prolonged gastrointestinal symptoms and weight loss who received intermittent anti-tubercular treatment and underwent operative interventions to relieve gastric outlet obstruction.The diagnosis chiefly relied on high-end examinations,like computed tomography scans and histopathological evaluation of postoperatively resected bowel tissue,which wasn't preceded by an all-inclusive stepwise primary pulmonary tuberculosis exclusion approach that usually begins with a detailed tuberculosis-pertinent history acquisition.Given the geographic locations where the patient had been(and/or treated),pivotal consideration of tuberculosis-associated endemicities in those regions,like human immunodeficiency virus(HIV)infection,might have improved the case description.The obtainment of HIV-relevant histories,like intravenous drug use and sexual practice,are good places to start.The sputum bacteriology also seems imperative to rule out atypical Mycobacterium species infection because of its clinico-radiohistopathological resemblance with pulmonary Mycobacterium tuberculosis.Altogether,this editorial aims to underscore that primary extrapulmonary tuberculosis diagnosis should comprise an elaborative,comprehensive,systematic,and stepwise primary pulmonary Mycobacterium tuberculosis exclusion workup.

Effectiveness of Histopathological Examination of Ultrasound-guided Puncture Biopsy Samples for Diagnosis of Extrapulmonary Tuberculosis

Objective To evaluate the diagnostic value of histopathological examination of ultrasound-guided puncture biopsy samples in extrapulmonary tuberculosis(EPTB).Methods This study was conducted at the Shanghai Public Health Clinical Center.A total of 115patients underwent ultrasound-guided puncture biopsy,followed by MGIT 960 culture(culture),smear,Gene Xpert MTB/RIF(Xpert),and histopathological examination.These assays were performed to evaluate their effectiveness in diagnosing EPTB in comparison to two different diagnostic criteria:liquid culture and composite reference standard(CRS).Results When CRS was used as the reference standard,the sensitivity and specificity of culture,smear,Xpert,and histopathological examination were(44.83%,89.29%),(51.72%,89.29%),(70.11%,96.43%),and(85.06%,82.14%),respectively.Based on liquid culture tests,the sensitivity and specificity of smear,Xpert,and pathological examination were(66.67%,72.60%),(83.33%,63.01%),and(92.86%,45.21%),respectively.Histopathological examination showed the highest sensitivity but lowest specificity.Further,we found that the combination of Xpert and histopathological examination showed a sensitivity of 90.80%and a specificity of 89.29%.Conclusion Ultrasound-guided puncture sampling is safe and effective for the diagnosis of EPTB.Compared with culture,smear,and Xpert,histopathological examination showed higher sensitivity but lower specificity.The combination of histopathology with Xpert showed the best performance characteristics.

The Retrospective Diagnostic Potential of Gene Xpert MTB/RIF for the Analysis of Formalin-Fixed Paraffin-Embedded Tissue from Extrapulmonary Tuberculosis Patients

Tuberculosis(TB)is a chronic disease caused by infection with Mycobacterium tuberculosis.Laboratory confirmation of this infection is challenging due to the paucibacillary nature of extrapulmonary tuberculosis(EPTB).

Evaluation of Xpert MTB/RIF Ultra for Diagnosis of Extrapulmonary Tuberculosis: A Retrospective Analysis in a Low-Tuberculosis Prevalence Setting

Background: Extrapulmonary tuberculosis (EPTB) remains difficult to diagnose because the clinical specimens to be examined are often paucibacillary and obtained with difficulty from inaccessible sites. An updated Xpert® MTB/RIF Ultra (Ultra) test has been designed and licensed to improve sensitivity in the detection of Mycobacterium tuberculosis complex. The aim of the present study is to evaluate the performance of Ultra assay for the clinical diagnosis of EPTB in a low tuberculosis prevalence country. Methods: A retrospective analysis was performed at “A. O dei Colli” of Naples on consecutive extrapulmonary specimens for EPTB across a three-year period. All different types of extrapulmonary specimens were tested for EPTB by smear microscopy, culture and Ultra assay in accordance with relevant guidelines. Results: A total of 606 EPTB samples, 561 culture negative EPTB and 45 culture positive EPTB were included. Using culture as reference standard, the overall sensitivities and specificities of Ultra assay were 95.6% (95% CI 84.8 - 99.5) and 97.5% (95% CI 95.8 - 98.6) respectively. Sensitivity and specificity of Ultra for individual category of specimens were also performed. Conclusion: In a low-tuberculosis prevalence setting, Ultra assay confirms to have a good performance in the diagnosis of EPTB for all different extrapulmonary samples.

Evaluation of Xpert MTB/RIF for the Diagnosis of Extrapulmonary Tuberculosis in China

We evaluate the performance of Xpert MTB/RIF for the diagnosis of extrapulmonary tuberculosis （EPTB） in China. The performance of Xpert was evaluated compared to the composite reference standard （CRS）, drug susceptibility testing （DST）, and imaging examination. The overall sensitivity and specificity of Xpert were 64.1% （195/304） and 100% （24/24）, respectively, using CRS as the gold standard. The sensitivity was significantly higher than that of culture for pus （P〈0.05）. The proportion of EPTB-positive cases diagnosed by imaging was two times more than that diagnosed using Xpert; however, 6 out of 19 cases may have been overdiagnosed by imaging.

Epidemiological perspective of drug resistant extrapulmonary tuberculosis

Tuberculosis(TB) remains one of the leading infectious diseases causing significant morbidity and mortality worldwide. Although, pulmonary TB is the most common presentation and is the main transmissible form of the disease, extrapulmonary TBalso significantly contributes to the burden of disease and can cause severe complications and disabilities. At present, the most serious issue with TB control programme is emergence of multi and extensively drug resistant Mycobacterium tuberculosis strain worldwide. As the number of drug resistant pulmonary TB is increasing around the world, the number of drug resistant TB with extrapulmonary manifestations are also on rise. However, there is surprisingly scant information in medical literatures on prevalence and impact of extrapulmonary drug-resistant TB. Here, we appraise the recent epidemiological studies that underpin the status and impact of drug resistance in TB cases with extrapulmonary manifestations.

Primary gastroduodenal tuberculosis presenting as gastric outlet obstruction:A case report and review of literature

BACKGROUND Mycobacterium tuberculosis(TB)is the causative agent of TB,a chronic granulo-matous illness.This disease is prevalent in low-income countries,posing a significant global health challenge.Gastrointestinal TB is one of the three forms.The disease can mimic other intra-abdominal conditions,leading to delayed diagnosis owing to the absence of specific symptoms.While gastric outlet obs-truction(GOO)remains a frequent complication,its incidence has declined with the advent of proton pump inhibitors and Helicobacter pylori eradication therapy.Gastroduodenal TB can cause upper gastrointestinal hemorrhage,obstruction,and malignancy-like tumors.CASE SUMMARY A 23-year-old male presented with recurrent epigastric pain,distension,nausea,vomiting,and weight loss,prompting a referral to a gastroenterologist clinic.Endoscopic examination revealed distorted gastric mucosa and signs of chronic inflammation.However,treatment was interrupted,possibly owing to vomiting or comorbidities such as human immunodeficiency virus infection or diabetes.Subsequent surgical intervention revealed a dilated stomach and diffuse thickening of the duodenal wall.Resection revealed gastric wall effacement with TB.CONCLUSION Primary gastric TB is rare,frequently leading to GOO.Given its rarity,suspicions should be promptly raised when encountering relevant symptoms,often requiring surgical intervention for diagnosis and treatment.

Unveiling the Threat: Case Reports of Extra-Pulmonary Tuberculosis among Sanctuary Chimpanzees

Primate sanctuaries across Africa play a pivotal role in the rescue and rehabilitation of confiscated and rescued wild primates, many of whom have had extensive contact with humans prior to their arrival and throughout the rehabilitation process, heightening the risk of disease transmission. While tuberculosis is not naturally occurring in free-living chimpanzees, it has been extensively observed in captive primates that have been in close proximity to humans or other captive primates infected with Mycobacterium tuberculosis. This case report delves into an outbreak of extra-pulmonary tuberculosis among juvenile chimpanzees within a sanctuary, detailing the associated diagnostic challenges and treatment approaches. The five cases had close contact with a caregiver infected with tuberculosis, subsequently transmitting the infection to other in-contact chimpanzees. Prolonged treatment, employing the human protocol of quadri-therapy (rifampicin, isoniazid, pyrazinamide, and ethambutol), followed by bi-therapy (rifampicin and isoniazid), resulted in complete resolution for all five cases. These cases underscore the critical importance of maintaining high levels of biosecurity, implementing effective quarantine measures, and adhering to strict hygiene practices when working with non-human primates.

A Case of Extrapulmonary Tuberculosis in an Immunocompetent Patient

Background: Primary cutaneous tuberculosis is a relatively uncommon manifestation especially in immunocompetent patients and it may occur in countries where tuberculosis is endemic. Findings: In this report, we described a case of a 20-year-old male presenting ulcerative lesions in the left foot and in the right hand caused by Mycobacterium tuberculosis without past history of pulmonary tuberculosis. Conclusion: This case report emphasizes the importance to suspect of a tuberculosis infection in all patients with skin lesions who do not respond to antibiotic treatment.

Recurrent Parotitis: Extrapulmonary Manifestation of Childhood Tuberculosis

Recurrent parotitis of childhood is a rare condition involving the largest salivary gland. The aetiology is multi-factorial and is usually non-obstructive or non-suppurative type of inflammation. It involves recurrent swelling of the parotid gland unilaterally or bilaterally over a period of months to years. Tuberculosis rarely involves the parotid gland, however in developing countries where tuberculosis prevalence is very high, any child with recurrent parotitis should be investigated for the same. We hereby, describe a 2 and half-year-old female child with recurrent parotid gland swelling below the right ear since 6 months. The swelling was acute in onset, gradually increasing in size with no discharge or pain. There was no history of fever, cough, cold, dryness of mouth or eyes, joint pain or rashes. There was history of koch’s contact in the maternal grandfather. A positive mantoux test and significant cervical lymphandenaopathy on Computed Tomography scan was noted. Common causes of recurrent parotitis, i.e. sjogrens syndrome, immunodeficiency and obstruction were ruled out. On the basis of the above history and investigations, the child was diagnosed as tuberculous parotitis.

Interferon-gamma release assays as a tool for differential diagnosis of gastrointestinal tuberculosis

In this editorial,we comment on an article published in a recent issue of the World Journal of Clinical Cases.There is a pressing need for reliable tools for diagnosing tuberculosis(TB)of the gastrointestinal tract.Despite advancements in the diagnosis and treatment,TB remains a global health challenge.Ali et al demon-strated that TB may mimic gastrointestinal conditions,such as gastric outlet obstruction,causing a delay in the diagnosis.Furthermore,the latter complication is frequently observed during infections,including Helicobacter pylori,and rarely is related to TB,as in the presented case.In line with this,we think that laboratory tests based on interferon-gamma release assays can be a helpful tool for diagnosing latent TB paced in the gastrointestinal tract.Innovative strategies and approaches for diagnosing latent/active extra pulmonary TB are crucial for establishing the diagnosis early and enhancing treatment strategies to mitigate the global burden of TB.

psk1 virulence gene-induced pulmonary and systemic tuberculosis in a young woman with normal immune function:A case report

BACKGROUND Tuberculosis is a chronic infectious disease and an important public health pro-blem.Despite progress in controlling tuberculosis,the incidence of tuberculosis in China is still very high,with 895000 new cases annually.This case report des-cribes the investigation of a case of severe disseminated tuberculosis in a young adult with normal immune function,conducted to ascertain why a Mycobacterium tuberculosis(M.tuberculosis)strain caused such severe disease.CASE SUMMARY A previously healthy 28-year-old woman presented to our hospital with a 1-mo-nth history of fever and fatigue.She was diagnosed with severe disseminated pulmonary tuberculosis,spinal tuberculosis with paravertebral abscesses,and tuberculous meningitis.M.tuberculosis was isolated from bronchoal-veolar lavage fluid.She was treated with standard antituberculous therapy and underwent debridement,bone graft,and internal fixation surgery for spinal tuberculosis.She responded to therapy and regained her ability to walk following the surgery.We analysed the whole-genome sequence of the strain and designated it BLM-A21.Additional M.tuberculosis genomes were selected from the Virulence Factor Database(http://www.mgc.ac.cn/cgi-bin/VFs/genus.cgi?Genus=Mycobacterium)for comparison.An evolutionary tree of the BLM-A21 strain was built using PhyML maximum likelihood software.Further gene analysis revealed that,except for the pks1 gene,BLM-A21 had similar virulence genes to the CDC 1551 and H37Rv strains,which have lower dissemination.CONCLUSION We speculate that the pks1 virulence gene in BLM-A21 may be the key virulence gene responsible for the wide-spread dissemination of M.tuberculosis infection in this previously healthy adult with normal immune function.

Revisiting tuberculosis as a cause of gastric outlet obstruction:Insights from a case report

Gastroduodenal tuberculosis(GD-TB)is exceptionally rare.The clinical manifestations of gastrointestinal TB are diverse and non-specific,which makes diagnosis difficult,leading to delayed diagnosis and high mortality.As a peer-reviewer of World Journal of Clinical Cases,I would like to share my opinion on the article published by this journal.The patient had no family history of TB or contact with people with TB.Primary GD-TB presenting as gastric outlet obstruction and normal findings of thoracic computed tomography increased the difficulty of diagnosis and treatment in this patient.The diagnosis and treatment scheme of this typical case have reference value for the clinical treatment of GD-TB.

Perianal tuberculous ulcer with active pulmonary,intestinal and orificial tuberculosis:A case report

BACKGROUND Orificial tuberculosis is a rare type of tuberculosis,which is easy to be misdiagnosed,and can cause great damage to the perianal skin and mucosa.Early diagnosis can avoid further erosion of the perianal muscle tissue by tuberculosis bacteria.CASE SUMMARY Here,we report a case of disseminated tuberculosis in a 62-year-old male patient with a perianal tuberculous ulcer and active pulmonary tuberculosis,intestinal tuberculosis and orificial tuberculosis.This is an extremely rare case of cutaneous tuberculosis of the anus,which was misdiagnosed for nearly a year.The patient received conventional treatment in other medical institutions,but specific treatment was delayed.Ultimately,proper diagnosis and treatment with standard anti-tuberculosis drugs for one year led to complete cure.CONCLUSION For skin ulcers that do not heal with repeated conventional treatments,consider ulcers caused by rare bacteria,such as Mycobacterium tuberculosis.

Profile of Extra-Pulmonary Tuberculosis in Internal Medicine

Introduction: Tuberculosis is an infectious disease that mainly affects the lung. Extrapulmonary localizations are a reason for hospitalization in our health facilities. The objective of this study was to describe the epidemiological, clinical, paraclinical and evolutionary aspects of extra pulmonary tuberculosis (EPT) at the Abass Ndao Hospital Center. Patients and Methods: This was a descriptive cross-sectional study conducted over a period of 11 years (January 1, 2010 to December 30, 2021). All patients with extrapulmonary tuberculosis hospitalized in the department of internal medicine during the recruitment period were included. Results: Fifty-two (52) patients were collected. The year 2019 recorded the most cases 23.08% (n = 20). The mean age of the patients was 40.56 ± 18.24 years. The age group 20 - 34 years 42.31% (n = 22) was the most represented. Females were in the majority 61.54% (n = 32) with a sex ratio (M/F) was 0.63. Housewives were in the majority 40.38% (n = 21). 60.87% of the cases (n = 14) came from a health facility. 38.46% of the cases had been infected. 21.74% (n = 9) were smokers. The reasons for consultation were dominated by fever (67.44%), AEG (62.79%) and cough (41.86%). Eighteen patients (40.91%) had fever. The mean time to consultation was 77.37 ± 90.3 days with extremes of 3 and 365 days. The median was 45 days. More than half of the patients 61.90% (n = 26) had anemia. Positive retroviral serology was noted in 21.43% of cases. All patients had a CRP greater than 6. More than half of the patients 51.92% (n = 27) had multifocal tuberculosis. The peritoneum 44.23% (n = 23) was the main organ affected. The average hospital stay was 9.8 ± 4.9 days with extremes of 1 and 19 days. All patients had received the protocol in force at the national level. Death was noted in 4 patients (9.52%). Conclusion: EPT is characterized in our context by a notorious diagnostic difficulty due to the multiplicity of clinical presentations, the complexity of explorations, and the problems of differential diagnosis notably with other granulomatosis, systemic lupus and cancers. This difficulty is reflected in the low rate of diagnosis with a paraclinical argument of certainty and in the long diagnostic delays.

From immunology to artificial intelligence: revolutionizing latent tuberculosis infection diagnosis with machine learning

Latent tuberculosis infection(LTBI)has become a major source of active tuberculosis(ATB).Although the tuberculin skin test and interferon-gamma release assay can be used to diagnose LTBI,these methods can only differentiate infected individuals from healthy ones but cannot discriminate between LTBI and ATB.Thus,the diagnosis of LTBI faces many challenges,such as the lack of effective biomarkers from Mycobacterium tuberculosis(MTB)for distinguishing LTBI,the low diagnostic efficacy of biomarkers derived from the human host,and the absence of a gold standard to differentiate between LTBI and ATB.Sputum culture,as the gold standard for diagnosing tuberculosis,is time-consuming and cannot distinguish between ATB and LTBI.In this article,we review the pathogenesis of MTB and the immune mechanisms of the host in LTBI,including the innate and adaptive immune responses,multiple immune evasion mechanisms of MTB,and epigenetic regulation.Based on this knowledge,we summarize the current status and challenges in diagnosing LTBI and present the application of machine learning(ML)in LTBI diagnosis,as well as the advantages and limitations of ML in this context.Finally,we discuss the future development directions of ML applied to LTBI diagnosis.

Recognizing and addressing the challenges of gastrointestinal tuberculosis

In this editorial,we comment on the article by Ali et al published in the recent issue of the World Journal of Clinical Cases.This case report shed light on a particularly rare manifestation of this disease-primary gastrointestinal tuberculosis(GTB)presenting as gastric outlet obstruction.GTB presents diagnostic challenges due to its nonspecific symptoms and lack of highly accurate diagnostic algorithms.This editorial synthesizes epidemiological data,risk factors,pathogenesis,clinical presentations,diagnostic methods,and therapies to raise awareness about GTB.GTB constitutes 1%-3%of all tuberculosis cases globally,with 6%-38%of patients also having pulmonary tuberculosis.Pathogenesis involves various modes of Mycobacterium tuberculosis complex entry into the gastrointestinal system,with the terminal ileum and ileocecal valve commonly affected.Clinical presentation varies,often resembling other intra-abdominal pathologies,necessitating a high index of suspicion.Diagnostic tools include a combination of biochemical,microbiological,radiological,and endoscopic assessments.Antitubercular medication remains the cornerstone of treatment,supplemented by surgical intervention in severe cases.Multidisciplinary management involving gastroenterologists,surgeons,pulmonologists,and infectious disease specialists is crucial for optimal outcomes.Despite advancements,timely diagnosis and management challenges persist,underscoring the need for continued research and collaboration in addressing primary GTB.

Clinical effects of detailed nursing management interventions on medication adherence and disease perception in patients with drugresistant tuberculosis

BACKGROUND Tuberculosis(TB)is a chronic respiratory infectious disease that considerably jeopardizes human health,and there is no effective vaccine suitable for its prevention in the entire population.AIM To investigate the promotion of medication adherence and disease cognition in patients with drug-resistant(DR-)TB using detailed nursing management.METHODS In total,114 patients with DR-TB who were diagnosed and treated at our hospital between January 2019 and January 2023 were included in this study.Patients in the control group(n=57)were managed with conventional nursing care,while those in the observation group(n=57)were managed with detailed nursing care.Medication adherence,disease awareness scores,medication safety,and nursing satisfaction were compared between the two groups after the intervention.RESULTS The post-intervention medication compliance rate was 91.23%in the observation group and 75.44%in the control group,with the former being 15.79%higher than the latter(P<0.05).There was no statistically significant difference in the disease awareness scores between the two groups before the intervention;the disease awareness scores of the observation group were significantly higher than those of the control group after the intervention(P<0.05).The incidence of gastrointestinal reactions,joint swelling and pain,hearing loss,electrolyte disorders,and liver and kidney function abnormalities were lower in the observation group than those in the control group.The total nursing satisfaction of the observation group was higher than that of the control group(P<0.05).CONCLUSION Implementation of detailed nursing management for patients with DR-TB can effectively improve medication adherence,enhance awareness of the disease,ensure safety of medication,and improve satisfaction with nursing care.

Community Caregivers’ Experiences and Programmatic Strategies to Improve Active Case Finding in Community Tuberculosis Care in Botswana 2016-2021

Background: The community tuberculosis care program was started to reduce the impact of TB and increase successful treatment outcomes, thus contributing to meeting WHO targets on TB. According to the Botswana Ministry of Health, community tuberculosis care was introduced with the main goal of reducing tuberculosis-related morbidity and mortality among communities through the expansion of direct observed therapy and community involvement to community settings. The community caregivers were to support tuberculosis patients throughout their treatment period until they were cured or had completed their treatment. Settings: Two major cities of Botswana, Francistown and Gaborone, with more than twenty-two health clinics offering tuberculosis care. Objective: To investigate community caregivers’ experiences and identify programmatic strategies to improve active TB case findings under the community TB care (CTBC) program in Botswana during 2016-2021. Methods: We adopted a descriptive qualitative research design, followed by convenience purposive sampling. We obtained consent and interviewed 40 participants who met the inclusion criteria, 16 out of 73 in Gaborone and 24 out of 38 from Francistown. Results: We interviewed 40 caregivers with a mean age of 43.4 years. Accepting the caregiving role was identified as the main experience by more than two thirds of the caregivers. While at least more than two-fifth felt obligated to care for the patient at home due to personal relations. More than half of the respondents found caregiving difficult or frustrating due to some challenges encountered during the caregiving role. Behavioral modifications were suggested under different subthemes as strategies to improve active case finding. [-rId13-]Conclusion: Acceptance was the major experience in CTBC. Intensification of known programmatic strategies was suggested by caregivers to improve tuberculosis active case finding in CTBC.