Extrapulmonary Infection Research Articles

57 Ocular tuberculosis: a differential for chronic panuveitis

Background Mycobacterium tuberculosis is an organism responsible for causing chronic granulomatous inflammation leading to active or latent tuberculosis (TB). Both pulmonary and extrapulmonary infections; including the skin, the eye, the cardiovascular, genitourinary and gastrointestinal systems can occur. Within the eye, it can cause global disease ranging from anterior or posterior uveitis to retinal TB. Within this abstract we demonstrate a case of chronic panuveitis with a diagnosis of ocular TB.MethodologyRetrospective chart reviewResultsWe reviewed a 9-year-old- male in the rheumatology outpatient clinic who was on treatment for ocular TB with methotrexate 2.5 mg once a week, prednisone 5 mg once a day, maxitrol eye drops once a day and prednisolone eye drops twice a day.He presented with a red, painless left eye with deteriorating vision 2 years ago. Functional enquiry was unremarkable. He was noted to have a fixed dilated left pupil at 3-4mm but other examinations were normal. Extensive investigations were carried out, including an Interferon-gamma release assay (IGRA)- which was positive. Toxoplasma antibody test, Treponema pallidum Haemagglutination test, and chest X-ray were all negative. He was then started on the above-mentioned therapies with marked improvement.A decision on increasing the methotrexate dose if steroid tapering showed no improvement was undertaken and a plan on reassessing the patient with ANA, ACE and HLA B51 was made, to ensure complete workup.Discussion and conclusionIntra or extra ocular TB (OTB) manifestations may result as a direct inoculation of the organism in ocular fluid or as a systemic immune response initiated by an infection from a distant site. There is a myriad of ocular manifestations of OTB which make forming a clinical diagnostic criterion difficult. The gold standard for diagnosis is an ocular fluid culture showing organisms but the yield may be low and the risk of damage to surrounding structures may be high. PCR tests done on the sample may yield clinical information but non ocular tests, such as the IGRA and tuberculin tests may also be employed. Therapy depends on active vs latent disease and mainly involves anti-inflammatory agents and anti-TBs.Ocular TB may lead to sudden and irreversible blindness with high socioeconomic implications and hence, an index of suspicion in areas with a high disease burden should be kept as diagnosis poses a challenge.

S2917 Acute Alcoholic Hepatitis With Portal Hypertension Complicated by Tuberculous Peritonitis and Ascites

Introduction: Peritonitis related to tuberculosis (TB) infection is rare in the US and normally associated with immunocompromised states. We present a patient found to have TB peritonitis during evaluation of alcoholic hepatitis without evident lung disease. Case Description/Methods: The patient is a 39 yo male born in Mexico with no medical history who presented with three days of abdominal distention, jaundice, and fevers in the setting of alcohol use disorder. He had no other historic risk factors for TB or cough. Exam was remarkable for a distended abdomen. Laboratory results showed leukocytosis, total bilirubin 3.5 (mg/dL), alkaline phosphatase 295 (U/L), AST 147 (U/L), ALT 62 (U/L), and positive quantiferon gold. Chest x-ray had no pulmonary lesions. Ascites fluid studies were significant for high white count (2214 k/uL) with lymphocytic predominance (91%). The serum ascites albumin gradient was consistent with portal hypertension, and ascites total protein was elevated (3.6 g/dL). Fluid ADA was positive. Cross sectional imaging of the abdomen showed omental caking, peritoneal lining nodularity, and hepatosplenomegaly. Fine needle aspiration of the peritoneum showed necrotizing and non-necrotizing granulomas. Sputum gram stain was negative for acid fast bacilli although sputum and ascites cultures ultimately grew TB (Figure). The patient was started on rifampin, isoniazid, pyrazinamide and ethambutol for TB and abstained from further alcohol use. Three months after discharge, jaundice and ascites had resolved and his liver tests had significantly improved. Discussion: TB peritonitis makes up 4-10% of extrapulmonary TB infections. Though rare in the US, it has a high mortality rate (50-60%). Diagnosis can be complicated by difficulty isolating the organism and culture results can take weeks. TB peritonitis can be supported by ascites fluid studies with elevated lymphocyte count, total protein, and positive ADA; although for more definitive diagnosis peritoneal biopsy should be considered. This patient represents a unique confluence of portal hypertension related ascites, induced by acute alcoholic hepatitis, along with TB peritonitis. It is possible that transient immunosuppression from alcoholic hepatitis served as a risk factor in reactivation and dissemination of latent TB. An index of suspicion for TB infection, based on his foreign birth, along with his abnormal ascites fluid studies, led to the peritoneal biopsy and ultimate culture diagnosis of his infection that might otherwise have been overlooked.Figure 1.: Nodularity of the peritoneal lining.

Application of metagenomic next-generation sequencing in cutaneous tuberculosis.

Tuberculous infection in a skin wound is a rare but well-known condition. This study describes a child infected with tuberculosis after being wounded. Because of swelling and pain in his wrist tissue, he was admitted to the Affiliated Hospital of Jining Medical University of Shandong Province on 16 October 2021. His medical history only included a wound. He was discharged after debridement. The laboratory data were normal. Two months after surgery, his wound was still swollen and painful. Secretions from the wound were sent for metagenomic next-generation sequencing (mNGS), which revealed three reads related to the Mycobacterium tuberculosis complex group (MTBC). A diagnosis of cutaneous tuberculosis (TB) was made. The wound disappeared after anti-TB drugs were administered. This case demonstrates that, while TB presenting as a severe cutaneous wound is rare, it should be considered in the clinical diagnosis. Clinicians should also pay attention to extrapulmonary infection with MTBC in patients, particularly in some long-suffering patients, and identify the specific pathogen as soon as possible. mNGS could help to identify pathogens and facilitate early treatment, thereby improving the prognosis.

A Positron Emission Tomography Tracer Targeting the S2 Subunit of SARS-CoV-2 in Extrapulmonary Infections.

Tracking the pathogen of coronavirus disease 2019 (COVID-19) in live subjects may help estimate the spatiotemporal distribution of SARS-CoV-2 infection in vivo. This study developed a positron emission tomography (PET) tracer of the S2 subunit of spike (S) protein for imaging SARS-CoV-2. A pan-coronavirus inhibitor, EK1 peptide, was synthesized and radiolabeled with copper-64 after being conjugated with 1,4,7-triazacyclononane-1,4,7-triyl-triacetic acid (NOTA). The in vitro stability tests indicated that [64Cu]Cu-NOTA-EK1 was stable up to 24 h both in saline and in human serum. The binding assay showed that [64Cu]Cu-NOTA-EK1 has a nanomolar affinity (Ki = 3.94 ± 0.51 nM) with the S-protein of SARS-CoV-2. The cell uptake evaluation used HEK293T/S+ and HEK293T/S– cell lines that showed that the tracer has a high affinity with the S-protein on the cellular level. For the in vivo study, we tested [64Cu]Cu-NOTA-EK1 in HEK293T/S+ cell xenograft-bearing mice (n = 3) and pseudovirus of SARS-CoV-2-infected HEK293T/ACE2 cell bearing mice (n = 3). The best radioactive xenograft-to-muscle ratio (X/Nxenograft 8.04 ± 0.99, X/Npseudovirus 6.47 ± 0.71) was most evident 4 h postinjection. Finally, PET imaging in the surrogate mouse model of beta-coronavirus, mouse hepatic virus-A59 infection in C57BL/6 J mice showed significantly enhanced accumulation in the liver than in the uninfected mice (1.626 ± 0.136 vs 0.871 ± 0.086 %ID/g, n = 3, P < 0.05) at 4 h postinjection. In conclusion, our experimental results demonstrate that [64Cu]Cu-NOTA-EK1 is a potential molecular imaging probe for tracking SARS-CoV-2 in extrapulmonary infections in living subjects.

POS-086 EPIDEMIOLOGY AND OUTCOMES OF EXTRA-PULMONARY FUNGAL INFECTIONS AMONG RENAL TRANSPLANT RECIPIENTS (A TERTIARY CARE EXPERIENCE)

The fungal infections cause a significant morbidity and mortality. With the advances in post-transplant care leading to improved graft and patient survival, the incidence has also increased. The published data regarding extra-pulmonary fungal infection is few and lacking.

POS-046 A RARE CASE OF AUTOCHTHONOUS DISSEMINATED BLASTOMYCOSIS INVOLVING BILATERAL KIDNEYS FROM INDIA - A GREAT MASQUERADE OF RENAL CELL CARCINOMA

Blastomyces dermatidis is an endemic fungus often seen in parts of the midwestern and south-central United States and Canada.Blastomycosis is an indolent systemic pyogranulomatous disease usually remains localised to the lungs, 25%–40% of those infected will develop extra-pulmonary infection manifested by cutaneous, osteoarticular, genitourinary (prostate and epididymis are commonly involved), or CNS disease in the decreasing order of involvement. Here we are presenting a rare case of disseminated blastomycosis with involvement of bilateral kidneys from India.

Lest we forget spinal tuberculosis (Potts's spine): Case series with unusual presentation

Pott's disease, also known as TB spondylitis, is a very uncommon extrapulmonary infection caused by Mycobacterium tuberculosis. As its prevalence is not high it can easily be underdiagnosed. Magnetic resonance imaging (MRI), computed tomographic (CT) guided needle aspiration, or biopsy are known to be the best techniques for early histopathological diagnosis along with confirmation by microbiological results. Ziehl Neelson stain (ZN) can detect Mycobacterium infections when clinically suspected samples are adequate and optimally stained. No single method or simple guideline can diagnose spinal tuberculosis. Early diagnosis and prompt treatment are necessary to prevent permanent neurological disability and to minimize spinal deformity. We are reporting three cases of Potts disease which could have been easily missed if we would have relied on one single investigation.

Case report of arthritis caused by Legionella anisa and review of the literature

BackgroundLegionella spp. is recognized as a common cause of community acquired pneumonia, with Legionella pneumophila serogroup 1 being the most prevalent. At least 70 species are described so far but few are identified in pathogenic conditions. Data on extrapulmonary infections are scarce.Case presentationA 73-yar-old male with chronic lymphoid leukemia was hospitalized for an insidious wrist arthritis. Ultrasound of the wrist showed a carpal and radiocarpal fluid effusion with positive Doppler signal. While routine bacterial cultures remained sterile, 16S rRNA PCR identified Legionella anisa. Ciprofloxacin 500 mg twice a day for a period of six weeks improved arthritis with full recovery at the end of the treatment.ConclusionLegionella non pneumophila are a rare cause of septic arthritis especially found in immunosuppressed patients and identification of species could help clinician to adapt antibiotherapy.

Pulmonary Microbial Composition in Sepsis-Induced Acute Respiratory Distress Syndrome.

Background: Acute respiratory distress syndrome (ARDS) is an unresolved challenge in the field of respiratory and critical care, and the changes in the lung microbiome during the development of ARDS and their clinical diagnostic value remain unclear. This study aimed to explore the role of the lung microbiome in disease progression in patients with sepsis-induced ARDS and potential therapeutic targets. Methods: Patients with ARDS were divided into two groups according to the initial site of infection, intrapulmonary infection (ARDSp, 111 cases) and extrapulmonary infection (ARDSexp, 45 cases), and a total of 28 patients with mild pulmonary infections were enrolled as the control group. In this study, we sequenced the DNA in the bronchoalveolar lavage fluid collected from patients using metagenomic next-generation sequencing (mNGS) to analyze the changes in the lung microbiome in patients with different infectious site and prognosis and before and after antibiotic treatment. Results: The Shannon–Wiener index indicated a statistically significant reduction in microbial diversity in the ARDSp group compared with the ARDSexp and control groups. The ARDSp group was characterized by a reduction in microbiome diversity, mainly in the normal microbes of the lung, whereas the ARDSexp group was characterized by an increase in microbiome diversity, mainly in conditionally pathogenic bacteria and intestinal microbes. Further analysis showed that an increase in Bilophila is a potential risk factor for death in ARDSexp. An increase in Escherichia coli, Staphylococcus aureus, Candida albicans, enteric microbes, or conditional pathogens may be risk factors for death in ARDSp. In contrast, Hydrobacter may be a protective factor in ARDSp. Conclusion: Different initial sites of infection and prognoses are likely to affect the composition and diversity of the pulmonary microbiome in patients with septic ARDS. This study provides insights into disease development and exploration of potential therapeutic targets.

A Comprehensive Review and Update on Epidemiology, Symptomatology and Management of Nontuberculous Mycobacteria (NTM)

Nontuberculous mycobacteria (NTM) are free-living organisms ubiquitously present in the environment. In recent times, NTM gained much importance due to the increase in incidence globally. They are potential agents in causing both pulmonary and extrapulmonary infections in both immunocompromised and immunocompetent individuals. The problem arises when the possible NTM cases are misdiagnosed as drug-resistant tuberculosis (DR-TB). Hence, it is essential to correctly identify the NTMs causing disease due to two major reasons. One is to prevent clinicians from starting anti-tuberculous drugs and the other is that treatment regimen differs for certain NTM from tuberculosis. Apart from conventional methods like smear microscopy, culture, in the current era newer diagnostic modalities like matrix-assisted laser desorption of ionization-time of flight mass spectrometry (MALDI TOF MS), line probe assay, genomic sequencing, are used in referral laboratories which allows identification and speciation of the organism. A thorough literature search was done in PubMed, Google Scholar, Cochrane Library, Embase, Scopus on nontuberculous mycobacteria. The search keywords include nontuberculous mycobacteria, atypical mycobacteria, case reports, and original articles on NTM. In this review, we have summarised the current knowledge on epidemiology, pathogenesis, clinical features, and treatment of NTM.

Comparison of 8 versus 15days of antibiotic therapy for Pseudomonas aeruginosa ventilator-associated pneumonia in adults: a randomized, controlled, open-label trial.

Duration of antibiotic therapy for ventilator-associated pneumonia (VAP) due to non-fermenting Gram-negative bacilli (NF-GNB), including Pseudomonas aeruginosa (PA) remains uncertain. We aimed to assess the non-inferiority of a short duration of antibiotics (8days) vs. prolonged antibiotic therapy (15days) in VAP due to PA (PA-VAP). We conducted a nationwide, randomized, open-labeled, multicenter, non-inferiority trial to evaluate optimal duration of antibiotic treatment in PA-VAP. Eligible patients were adults with diagnosis of PA-VAP and randomly assigned in 1:1 ratio to receive a short-duration treatment (8days) or a long-duration treatment (15days). A pre-specified analysis was used to assess a composite endpoint combining mortality and PA-VAP recurrence rate during hospitalization in the intensive care unit (ICU) within 90days. The study was stopped after 24 months due to slow inclusion rate. In intention-to-treat population (n = 186), the percentage of patients who reached the composite endpoint was 25.5% (N = 25/98) in the 15-day group versus 35.2% (N = 31/88) in the 8-day group (difference 9.7%, 90% confidence interval (CI) -1.9%-21.2%). The percentage of recurrence of PA-VAP during the ICU stay was 9.2% in the 15-day group versus 17% in the 8-day group. The two groups had similar median days of mechanical ventilation, of ICU stay, number of extra pulmonary infections and acquisition of multidrug-resistant (MDR) pathogens during ICU stay. Our study failed to show the non-inferiority of a short duration of antibiotics in the treatment of PA-VAP, compared to a long duration. The short duration strategy may be associated to an increase of PA-VAP recurrence. However, the lack of power limits the interpretation of this study.

Case Report Tuberculous Spondylitis in Elderly with Polyneuropathy

Background Tuberculous (TB) spondylitis or Pott’s Disease is a manifestation of extrapulmonary tuberculosis infection caused by the hematogenous and lymphomatous spread of Mycobacterium Tuberculosis, causing infection in the vertebral bones. Approximately 10% of extrapulmonary TB cases are TB spondylitis. Pulmonary and extrapulmonary tuberculosis cases are considerable cases in developing countries. Indonesia is a country with the third-highest prevalence of TB in the world after China and India.Objective The aim of this study was to report a case of TB spondylitis in a 66 years old woman with polyneuropathy at Bethesda Hospital Yogyakarta.Case description A 66 years old female patient presented with complaints of pain and difficulty in moving the left lower limb 3 months ago. The patient had a history of hypertension 5 years ago, while the family history was not specific. The patient was generally in pain with full awareness and cooperation. Vital sign examination showed blood pressure 140/80 mmHg, pulse 82 beats per minute, and respiratory rate of 22 breaths per minute. The lumbosacral-MRI examination was performed without contrast material and L2-L5 TB Spondylitis, with L2-L3 Disc protrusion, was found.Conclusion Tuberculous spondylitis (TB) may cause paradiscal inflammation, edema, and progressive bone destruction due to lysis of anterior bone tissue and secondary ischemia which will lead to collapse. Pain, difficulty moving, and local swelling are the most common complaints. Abnormalities in the curvature, misalignment of the vertebrae, deformity and bone destruction might be found in MRI radiological imaging. Treatment of TB spondylitis prioritizes administering of anti-TB drugs combined with immobilization using a girdle. The prognosis for TB spondylitis varies depending on the clinical manifestations.

Epidemiology of extrapulmonary tuberculosis among pediatric inpatients in mainland China: a descriptive, multicenter study

ABSTRACT Pediatric tuberculosis (TB) is a serious infectious disease that affects many children worldwide and is more likely to be extrapulmonary than adult TB. However, the clinical and epidemiological profile, and cost burden of pediatric extrapulmonary TB (EPTB) in China remain unknown. Here, we conducted a descriptive, multicenter study of pediatric TB patients from 22 hospitals across all six regions in China from October 2015 to December 2018. Of 4,654 patients, 54.23% (2,524) had pulmonary TB (PTB), 17.76% (827) had EPTB, and 28.00% (1,303) had concurrent extrapulmonary and pulmonary TB (combined TB). Compared with PTB, EPTB and combined TB were associated with lower hospitalization frequency (2.43 and 2.21 vs. 3.16 times), longer length of stay (10.61 and 11.27 vs. 8.56 days), and higher rate of discharge against medical advice (8.46% and 9.44% vs. 5.67%). EPTB was associated with higher mortality (0.97% vs. 0.24% and 0.31%), higher rate of low birth weight (17.69% vs. 6.79% and 6.22%), worse diagnosis at the first visit (21.16% vs. 34.67% and 44.47%), and worse hospitalization plan situation (4.35% vs. 7.81% and 7.44%), compared with PTB and combined TB. EPTB and combined TB had higher financial burdens (17.67% and 16.94% vs. 13.30%) and higher rates of catastrophic expenditure (8.22% and 9.59% vs. 5.03%), compared with PTB. Meningitis TB (34.18%) was the most frequent form of total extrapulmonary infection and had the highest cost burden and rate of catastrophic expenditure. In conclusion, improved screening approaches for pediatric EPTB are needed to reduce diagnostic challenges and financial burden.

Tuberculosis extrapulmonar. Formas clínicas en pacientes en situaciones especiales

The term extrapulmonary tuberculosis is used to describe M. tuberculosis infection of any organ without demonstrated pulmonary involvement. On occasion, simultaneous pulmonary and extrapulmonary infection occurs, in which case it is classified as pulmonary tuberculosis. It represents 20% of all tuberculosis cases worldwide. Its incidence has increased since the 1980s as a result of HIV infection. The most frequently affected areas are the pleura, lymph nodes, kidney and urinary tracts, bones and joints, central nervous system (CNS), and abdomen. Symptoms will depend on the organ involved. It is always necessary to rule out concomitant lung infection. In order to diagnose it, the existence of mycobacteria must be demonstrated through staining, cultures, or nucleic acid amplification techniques in samples obtained via puncture or biopsy. It can also be diagnosed by means of caseating granulomas with central caseous necrosis. Treatment is generally the same as that of pulmonary tuberculosis except when there is CNS or bone and joint involvement, which require a longer treatment time. When there is CNS involvement, glucocorticoids must also be administered.

Intestinal Damage in COVID-19: SARS-CoV-2 Infection and Intestinal Thrombosis.

The intestinal tract, with high expression of angiotensin-converting enzyme 2 (ACE2), is a major site of extrapulmonary infection in COVID-19. During pulmonary infection, the virus enters the bloodstream forming viremia, which infects and damages extrapulmonary organs. Uncontrolled viral infection induces cytokine storm and promotes a hypercoagulable state, leading to systemic microthrombi. Both viral infection and microthrombi can damage the gut–blood barrier, resulting in malabsorption, malnutrition, and intestinal flora entering the blood, ultimately increasing disease severity and mortality. Early prophylactic antithrombotic therapy can prevent these damages, thereby reducing mortality. In this review, we discuss the effects of SARS-CoV-2 infection and intestinal thrombosis on intestinal injury and disease severity, as well as corresponding treatment strategies.

Characteristics of procalcitonin in hospitalized COVID-19 patients and clinical outcomes of antibiotic use stratified by procalcitonin levels.

We examined the characteristics of pro-calcitonin (PCT) in hospitalized COVID-19 patients (cohort 1) and clinical outcomes of antibiotic use stratified by PCT in non-critically ill patients without bacterial co-infection (cohort 2). Retrospective reviews were performed in adult, hospitalized COVID-19 patients during March–May 2020. For cohort 1, we excluded hospital transfers, renal disease and extra-pulmonary infection without isolated pathogen(s). For cohort 2, we further excluded microbiologically confirmed infection, ‘do not resuscitate ± do not intubate’ status, and intensive care unit (ICU). For cohort 1, PCT was compared between absent/low-suspicion and proven bacterial co-infections. Factors associated with elevated PCT and sensitivity/specificity/PPV/NPV of PCT cutoffs for identifying bacterial co-infections were explored. For cohort 2, clinical outcomes including mechanical ventilation within 5 days (MV5) were compared between the antibiotic and non-antibiotic groups stratified by PCT ≥ 0.25 µg/L. Nine hundred and twenty four non-ICU and 103 ICU patients were included (cohort 1). The median PCT was higher in proven vs. absent/low-suspicion of bacterial co-infection. Elevated PCT was significantly associated with proven bacterial co-infection, ICU status and oxygen requirement. For PCT ≥ 0.25 µg/L, sensitivity/specificity/PPV/NPV were 69/65/6.5/98% (non-ICU) and 75/33/8.6/94% (ICU). For cohort 2, 756/1305 (58%) patients were included. Baseline characteristics were balanced between the antibiotic and non-antibiotic groups except PCT ≥ 0.25 µg/L (antibiotic:non-antibiotic = 59%:24%) and tocilizumab use (antibiotic:non-antibiotic = 5%:2%). 23% (PCT < 0.25 µg/L) and 58% (PCT ≥ 0.25 µg/L) received antibiotics. Antibiotic group had significantly higher rates of MV5. COVID-19 severity inferred from ICU status and oxygen requirement as well as the presence of bacterial co-infections were associated with elevated PCT. PCT showed poor PPV and high NPV for proven bacterial co-infections. The use of antibiotics did not show improved clinical outcomes in COVID-19 patients with PCT ≥ 0.25 µg/L outside of ICU when bacterial co-infections are of low suspicion.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11739-022-02955-5.

Infection of liver hepatocytes with SARS-CoV-2.

Multi-organ disease in patients seriously unwell with COVID-19 is commonly reported. However, debate exists as to whether extra-pulmonary manifestations are the result of indirect effects or of direct extra-pulmonary organ infection. Wanner et al. attempt to tackle this issue with a focus on liver tropism of the SARS-CoV-2 virus.

Profile and histopathology features of top three cases of Extra Pulmonary Tuberculosis (EPTB) in West Nusa Tenggara: A retrospective cross-sectional study

BackgroundTuberculosis (TB) is an infectious disease that might threaten life with a high incidence rate globally, especially in developing countries such as Indonesia. Although some TB cases are found in the lungs, the incidence of patients with extra-pulmonary TB infection also shows a significant number. However, these cases are still underreported, especially in Indonesia. Histopathological examination is one of the gold standards for diagnosing EPTB. Materials and methodsThis is a cross-sectional retrospective descriptive study. This study uses data from medical records and histopathological examination results of extra-pulmonary TB patients at two hospitals in West Nusa Tenggara between May 2010 and February 2020. The inclusion criteria for this study were patients diagnosed with EPTB histopathologically and had complete paraffin block. In addition, the exclusion criteria were patients with incomplete data in the medical record. The data recorded include gender, age, organ location, area of residence, and histopathological features. ResultsThere were 1.817 cases of extra-pulmonary TB in West Nusa Tenggara from May 2010 to February 2020. The top three organs were from the neck (84.7%), breast (14.1%), and colon (1.2%), with a total of 1362 cases. Women dominate the top three cases of EPTB with 894 patients (65.7%) and in the age group 21–30 (28%). Central Lombok has the most EPTB patients (450; 33.07%). Microscopic examination revealed well-organized granulomas in 988 patients (72.6%) and poorly organized granulomas in 374 patients (27.4%). ConclusionThe three most frequent cases of EPTB found in West Nusa Tenggara are cervical lymphadenitis TB, mastitis TB, and colitis TB, with the majority of cases being well-organized granulomas. Further studies dealing with better designs and larger sample sizes need to be considered. The results of this study are significantly needed to determine the intervention strategies to reduce morbidity and mortality due to EPTB.

The source and fate of Mycobacterium tuberculosis complex in wastewater and possible routes of transmission

BackgroundThe Mycobacterium tuberculosis complex (MTBC) consists of causative agents of both human and animal tuberculosis and is responsible for over 10 million annual infections globally. Infections occur mainly through airborne transmission, however, there are possible indirect transmissions through a faecal-oral route which is poorly reported. This faecal-oral transmission could be through the occurrence of the microbe in environments such as wastewater. This manuscript, therefore, reviews the source and fate of MTBC in the wastewater environment, including the current methods in use and the possible risks of infections.ResultsThe reviewed literature indicates that about 20% of patients with pulmonary TB may have extra-pulmonary manifestations such as GITB, resulting in shedding in feaces and urine. This could potentially be the reason for the detection of MTBC in wastewater. MTBC concentrations of up to 5.5 × 105 (±3.9 × 105) copies/L of untreated wastewater have been reported. Studies have indicated that wastewater may provide these bacteria with the required nutrients for their growth and could potentially result in environmental transmission. However, 98.6 (± 2.7) %, removal during wastewater treatment, through physical-chemical decantation (primary treatment) and biofiltration (secondary treatment) has been reported. Despite these reports, several studies observed the presence of MTBC in treated wastewater via both culture-dependent and molecular techniques.ConclusionThe detection of viable MTBC cells in either treated or untreated wastewater, highlights the potential risks of infection for wastewater workers and communities close to these wastewater treatment plants. The generation of aerosols during wastewater treatment could be the main route of transmission. Additionally, direct exposure to the wastewater containing MTBC could potentially contribute to indirect transmissions which may lead to pulmonary or extra-pulmonary infections. This calls for the implementation of risk reduction measures aimed at protecting the exposed populations.

Probiotics: relevant during the coronavirus (COVID-19) infection pandemic?

The review presents modern views on the role of probiotics in the treatment and prevention of complications of the novel coronavirus COVID-19 infection. This infection can be complicated, for example, by the development of diarrhea after the use of antibacterial drugs in case of secondary bacterial infection, extrapulmonary viral infections, viremia, and the so-called «cytokine storm». The emphasis has been placed on such potentially beneficial effects of probiotics as а prevention of antibioticassociated diarrhea, prevention of intestinal damage induced directly by viral replication, prevention of leaky gut syndrome and immunomodulation in case of coronavirus COVID-19 infection. It has been shown that the use of probiotics alongside antibiotic therapy significantly reduces the risk of developing antibiotic-associated diarrhea, including such a severe variant as pseudomembranous colitis. The use of a probiotic during a viral respiratory disease reduces the risk of a severe disease course due to the positive modulation of inflammation and direct antiviral effects. Selected data showed the positive effect of probiotics on the tight junction stability of the intestine, which potentially protects against viremia and the penetration of immunogenic molecules into the internal environment of the body. In order to address the challenges adequately, a probiotic should meet certain requirements in terms of product quality, safety, evidence of efficacy, composition and understanding of the strains. The article presents data on the successful use of a multi-strain immuno-probiotic as an example demonstrating the therapeutic potential of modern multi-strain probiotics as a nonspecific immunomodulatory agent for the prevention of acute respiratory diseases.