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Testing for miliary tuberculosis is conducted in a similar manner as for other forms of tuberculosis, although a number of tests must be conducted on a patient to confirm diagnosis. Tests include chest x-ray, sputum culture, bronchoscopy, open lung biopsy, head CT/MRI, blood cultures, fundoscopy, and electrocardiography. The tuberculosis (TB) blood test, also called an Interferon Gamma Release Assay or IGRA, is a way to diagnose latent TB.
A variety of neurological complications have been noted in miliary tuberculosis patients—tuberculous meningitis and cerebral tuberculomas being the most frequent. However, a majority of patients improve following antituberculous treatment. Rarely lymphangitic spread of lung cancer could mimic miliary pattern of tuberculosis on regular chest X-ray.
The tuberculin skin test, commonly used for detection of other forms of tuberculosis, is not useful in the detection of miliary tuberculosis. The tuberculin skin test fails due to the high numbers of false negatives. These false negatives may occur because of higher rates of tuberculin anergy compared to other forms of tuberculosis.
If left untreated, miliary tuberculosis is almost always fatal. Although most cases of miliary tuberculosis are treatable, the mortality rate among children with miliary tuberculosis remains 15 to 20% and for adults 25 to 30%. One of the main causes for these high mortality rates includes late detection of disease caused by non-specific symptoms. Non-specific symptoms include: coughing, weight loss, or organ dysfunction. These symptoms may be implicated in numerous disorders, thus delaying diagnosis. Misdiagnosis with tuberculosis meningitis is also a common occurrence when patients are tested for tuberculosis, since the two forms of tuberculosis have high rates of co-occurrence.
The Mantoux tuberculin skin test is often used to screen people at high risk for TB. Those who have been previously immunized may have a false-positive test result. The test may be falsely negative in those with sarcoidosis, Hodgkin's lymphoma, malnutrition, and most notably, active tuberculosis. Interferon gamma release assays, on a blood sample, are recommended in those who are positive to the Mantoux test. These are not affected by immunization or most environmental mycobacteria, so they generate fewer false-positive results. However, they are affected by "M. szulgai", "M. marinum", and "M. kansasii". IGRAs may increase sensitivity when used in addition to the skin test, but may be less sensitive than the skin test when used alone.
Diagnosing active tuberculosis based only on signs and symptoms is difficult, as is diagnosing the disease in those who are immunosuppressed. A diagnosis of TB should, however, be considered in those with signs of lung disease or constitutional symptoms lasting longer than two weeks. A chest X-ray and multiple sputum cultures for acid-fast bacilli are typically part of the initial evaluation. Interferon-γ release assays and tuberculin skin tests are of little use in the developing world. Interferon gamma release assays (IGRA) have similar limitations in those with HIV.
A definitive diagnosis of TB is made by identifying "M. tuberculosis" in a clinical sample (e.g., sputum, pus, or a tissue biopsy). However, the difficult culture process for this slow-growing organism can take two to six weeks for blood or sputum culture. Thus, treatment is often begun before cultures are confirmed.
Nucleic acid amplification tests and adenosine deaminase testing may allow rapid diagnosis of TB. These tests, however, are not routinely recommended, as they rarely alter how a person is treated. Blood tests to detect antibodies are not specific or sensitive, so they are not recommended.
The most common organisms which cause lobar pneumonia are "Streptococcus pneumoniae", also called pneumococcus, "Haemophilus influenzae" and "Moraxella catarrhalis". "Mycobacterium tuberculosis", the tubercle bacillus, may also cause lobar pneumonia if pulmonary tuberculosis is not treated promptly.
Like other types of pneumonia, lobar pneumonia can present as community acquired, in immune suppressed patients or as nosocomial infection. However, most causative organisms are of the community acquired type.
Pathological specimens to be obtained for investigations include:
1. Sputum for culture, AAFBS and gram stain
2. Blood for full hemogram/complete blood count, ESR and other acute phase reactants
3. Procalcitonin test, more specific
The identification of the infectious organism (or other cause) is an important part of modern treatment of pneumonia. The anatomical patterns of distribution can be associated with certain organisms, and can help in selection of an antibiotic while waiting for the pathogen to be cultured.
Tuberculous pericarditis is a form of pericarditis.
Pericarditis caused by tuberculosis is difficult to diagnose, because definitive diagnosis requires culturing "Mycobacterium tuberculosis" from aspirated pericardial fluid or pericardial , which requires high technical skill and is often not diagnostic (the yield from culture is low even with optimum specimens). The Tygerberg scoring system helps the clinician to decide whether pericarditis is due to tuberculosis or whether it is due to another cause: night sweats (1 point), weight loss (1 point), fever (2 point), serum globulin > 40g/l (3 points), blood total leucocyte count <10 x 10/l (3 points); a total score of 6 or more is highly suggestive of tuberculous pericarditis. Pericardial fluid with an interferon-γ level greater than 50/ml is highly specific for tuberculous pericarditis.
There are no randomized trials which evaluate the length of anti-tuberculosis treatment required for tuberculous pericarditis. There is a small but not conclusive benefit for treatment with a schedule of steroids with anti-tuberculosis drugs. Open surgical drainage of fluid though effective in preventing cardiac tamponade was associated with more deaths.
The specific criteria for diagnosis of CPA are:
Chest X-rays showing one or more lung cavities. There may be a fungal ball present or not.
Symptoms lasting more than 3 months, usually including weight loss, fatigue, cough, coughing blood (haemoptysis) and breathlessness
A blood test or tissue fluid test positive for Aspergillus species
Aspergilloma
An aspergilloma is a fungal mass caused by a fungal infection with Aspergillus species that grows in either scarred lungs or in a pre-existing lung cavity, which may have been caused by a previous infection. Patients with a previous history of tuberculosis, sarcoidosis, cystic fibrosis or other lung disease are most susceptible to an aspergilloma. Aspergillomas may have no specific symptoms but in many patients there is some coughing up of blood called haemoptysis - this may be infrequent and in small quantity, but can be severe and then it requires urgent medical help.
Tests used to diagnose an aspergilloma may include:
- Chest X-ray
- Chest CT
- Sputum culture
- Bronchoscopy or bronchoscopy with lavage (BAL)
- Serum precipitins for aspergillus (blood test to detect antibodies to aspergillus)
Almost all aspergillomas are caused by "Aspergillus fumigatus". In diabetic patients it may be caused by "Aspergillus niger". It is very rarely caused by "Aspergillus flavus", "Aspergillus oryzae", "Aspergillus terreus" or "Aspergillus nidulans".
Treatment depends on the underlying cause. Treatments include iced saline, and topical vasoconstrictors such as adrenalin or vasopressin. Selective bronchial intubation can be used to collapse the lung that is bleeding. Also, endobronchial tamponade can be used. Laser photocoagulation can be used to stop bleeding during bronchoscopy. Angiography of bronchial arteries can be performed to locate the bleeding, and it can often be embolized. Surgical option is usually the last resort, and can involve, removal of a lung lobe or removal of the entire lung. Non–small-cell lung cancer can also be treated with erlotinib or gefitinib. Cough suppressants can increase the risk of choking.
Most cases of aspergilloma do not require treatment. Treatment of diseases which increase the risk of aspergilloma, such as tuberculosis, may help to prevent their formation. In cases complicated by severe hemoptysis or other associated conditions such as pleural empyema or pneumothorax, surgery may be required to remove the aspergilloma and the surrounding lung tissue by doing a lobectomy or other types of resection and thus stop the bleeding. There has been interest in treatment with antifungal medications such as itraconazole, none has yet been shown to reliably eradicate aspergillomata.
Although most fungi — especially "Aspergillus" — fail to grow in healthy human tissue, significant growth may occur in people whose adaptive immune system is compromised, such as those with chronic granulomatous disease, who are undergoing chemotherapy, or who have recently undergone a bone marrow transplantation. Within the lungs of such individuals, the fungal hyphae spread out as a spherical growth. With the restoration of normal defense mechanisms, neutrophils and lymphocytes are attracted to the edge of the spherical fungal growth where they lyse, releasing tissue-digesting enzymes as a normal function. A sphere of the infected lung is thus cleaved from the adjacent lung. This sphere flops around in the resulting cavity and is recognized on x-ray as a fungus ball. This process is beneficial as a potentially serious invasive fungal infection is converted into surface colonization. Although the fungus is inactivated in the process, surgeons may choose to operate to reduce the possibility of bleeding. Microscopic examination of surgically removed recently formed fungus balls clearly shows a sphere of dead lung containing fungal hyphae. Microscopic examination of older lesions reveals mummified tissue which may reveal faint residual lung or hyphal structures.
Conditions which commonly involve hemoptysis include bronchitis and pneumonia, lung cancers and tuberculosis. Other possible underlying causes include aspergilloma, bronchiectasis, coccidioidomycosis, pulmonary embolism, pneumonic plague, and cystic fibrosis. Rarer causes include hereditary hemorrhagic telangiectasia (HHT or Rendu-Osler-Weber syndrome), Goodpasture's syndrome, and granulomatosis with polyangiitis. In children, hemoptysis is commonly caused by the presence of a foreign body in the airway. The condition can also result from over-anticoagulation from treatment by drugs such as warfarin.
Blood-laced mucus from the sinus or nose area can sometimes be misidentified as symptomatic of hemoptysis (such secretions can be a sign of nasal or sinus cancer, but also a sinus infection). Extensive non-respiratory injury can also cause one to cough up blood. Cardiac causes like congestive heart failure and mitral stenosis should be ruled out.
The origin of blood can be identified by observing its color. Bright-red, foamy blood comes from the respiratory tract, whereas dark-red, coffee-colored blood comes from the gastrointestinal tract. Sometimes hemoptysis may be rust-colored.
The most common cause of minor hemoptysis is bronchitis.
- Lung cancer, including both non-small cell lung carcinoma and small cell lung carcinoma.
- Sarcoidosis
- Aspergilloma
- Tuberculosis
- Histoplasmosis
- Pneumonia
- Pulmonary edema
- Pulmonary embolism
- Foreign body aspiration and aspiration pneumonia
- Goodpasture's syndrome
- Granulomatosis with polyangiitis
- Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)
- Bronchitis
- Bronchiectasis
- Pulmonary embolism
- Anticoagulant use
- Trauma
- Lung abscess
- Mitral stenosis
- Tropical eosinophilia
- Bleeding disorders
- Hughes-Stovin Syndrome and other variants of Behçet's disease
- Squamous Cell Carcinoma Of Esophagus
A study conducted on 452 patients revealed that the genotype responsible for higher IL-10 expression makes HIV infected people more susceptible to tuberculosis infection. Another study on HIV-TB co-infected patients also concluded that higher level of IL-10 and IL-22 makes TB patient more susceptible to Immune reconstitution inflammatory syndrome (IRIS). It is also seen that HIV co-infection with tuberculosis also reduces concentration of immunopathogenic matrix metalloproteinase (MMPs) leading to reduced inflammatory immunopathology.
A Simon focus is a tuberculosis (TB) nodule that can form in the apex of the lung when a primary TB infection elsewhere in the body spreads to the lung apex via the bloodstream. Simon focus nodules are often calcified.
The initial lesion is usually a small focus of consolidation, less than 2cm in diameter and located within 1 to 2 cm of the apical pleura. In adolescence, Simon foci may become reactivated and develop into Assmann foci. Such foci are sharply circumscribed, firm, gray-white to yellow areas that have a variable amount of central caseation and peripheral fibrosis.
Alveolar disease is visible on chest radiography as small, ill-defined nodules of homogeneous density centered on the acini or bronchioles. The nodules coalesce early in the course of disease, such that the nodules may only be seen as soft fluffy edges in the periphery.
When the nodules are centered on the hilar regions, the chest x-ray may develop what is called the "butterfly," or "batwing" appearance. The nodules may also have a segmental or lobar distribution. Air alveolograms and air bronchograms can also be seen.
These findings appear soon after the onset of symptoms and change rapidly thereafter.
A segmental or lobar pattern may be apparent after aspiration pneumonia, atelectasis, lung contusion, localized pulmonary edema, obstructive pneumonia, pneumonia, pulmonary embolism with infarction, or tuberculosis.
An aspergilloma, also known as a "mycetoma or fungus ball"', is a clump of mold which exists in a body cavity such as a paranasal sinus or an organ such as the lung. By definition, it is caused by fungi of the genus "Aspergillus".
Cavitary pneumonia is a disease in which the normal lung architecture is replaced by a cavity. In a healthy lung, oxygen transport occurs at the level of the alveoli, each of which has an average size of 0.1 mm. These air spaces can become enlarged by a number of processes: bacterial infection (tuberculosis), fungal infection, vasculitis (granulomatosis with polyangiitis), collagen vascular disease (Sjögren's syndrome) or granulomatous disease (sarcoidosis).
A bronchopleural fistula (BPF) is a fistula between the pleural space and the lung. It can develop following Pneumonectomy, post traumatically, or with certain types of infection. It may also develop when large airways are in communication with the pleural space following a large pneumothorax or other loss of pleural negative pressure, especially during positive pressure mechanical ventilation. On imaging, the diagnosis is suspected indirectly on radiograph. Increased gas in the pneumonectomy operative bed, or new gas within a loculated effusion are highly suggestive of the diagnosis. Infectious causes include tuberculosis, "Actinomyces israelii", "Nocardia", and "Blastomyces dermatitidis". Malignancy and trauma can also result in the abnormal communication.
Controlling the spread of tuberculosis infection can prevent tuberculous spondylitis and arthritis. Patients who have a positive PPD test (but not active tuberculosis) may decrease their risk by properly taking medicines to prevent tuberculosis. To effectively treat tuberculosis, it is crucial that patients take their medications exactly as prescribed.
Patients with single aspergillomas generally do well with surgery to remove the aspergilloma, and are best given pre-and post-operative antifungal drugs. Often, no treatment is necessary. However, if a patient coughs up blood (haemoptysis), treatment may be required (usually angiography and embolisation, surgery or taking tranexamic acid). Angiography (injection of dye into the blood vessels) may be used to find the site of bleeding which may be stopped by shooting tiny pellets into the bleeding vessel.
For chronic cavitary pulmonary aspergillosis and chronic fibrosing pulmonary aspergillosis, lifelong use of antifungal drugs is usual. Itraconazole and voriconazole are first and second-line anti fungal agents respectively. Posaconazole can be used as third-line agent, for patients who are intolerant of or developed resistance to the first and second-line agents. Regular chest X-rays, serological and mycological parameters as well as quality of life questionnaires are used to monitor treatment progress. It is important to monitor the blood levels of antifungals to ensure optimal dosing as individuals vary in their absorption levels of these drugs.
This is a group of tests that use polymerase chain reaction (PCR) to detect mycobacterial nucleic acid. These test vary in which nucleic acid sequence they detect and vary in their accuracy. The two most common commercially available tests are the amplified mycobacterium tuberculosis direct test (MTD, Gen-Probe) and Amplicor. In 2007, review concluded that for diagnosing tuberculous meningitis "Individually, the AMTD test appears to perform the best (sensitivity 74% and specificity 98%)", they found the pooled prevalence of TB meningitis to be 29%.
Alveolar lung diseases, are a group of diseases that mainly affect the alveoli of the lungs.
Lobar pneumonia usually has an acute progression.
Classically, the disease has four stages:
- Congestion in the first 24 hours: This stage is characterized histologically by vascular engorgement, intra-alveolar fluid, small numbers of neutrophils, often numerous bacteria. Grossly, the lung is heavy and hyperemic
- Red hepatization or consolidation: Vascular congestion persists, with extravasation of red cells into alveolar spaces, along with increased numbers of neutrophils and fibrin. The filling of airspaces by the exudate leads to a gross appearance of solidification, or consolidation, of the alveolar parenchyma. This appearance has been likened to that of the liver, hence the term "hepatization".
- Grey hepatization: Red cells disintegrate, with persistence of the neutrophils and fibrin. The alveoli still appear consolidated, but grossly the color is paler and the cut surface is drier.
- Resolution (complete recovery): The exudate is digested by enzymatic activity, and cleared by macrophages or by cough mechanism. Enzymes produced by neutrophils will liquify exudates, and this will either be coughed up in sputum or be drained via lymph.
It is not practical to test or decontaminate most sites that may be contaminated with "H. capsulatum", but the following sources list environments where histoplasmosis is common, and precautions to reduce a person's risk of exposure, in the three parts of the world where the disease is prevalent. Precautions common to all geographical locations would be to avoid accumulations of bird or bat droppings.
The US National Institute for Occupational Safety and Health (NIOSH) provides information on work practices and personal protective equipment that may reduce the risk of infection. This document is available in English and Spanish.
Authors at the University of Nigeria have published a review which includes information on locations in which histoplasmosis has been found in Africa (in chicken runs, bats and the caves bats infest, and in soil), and a thorough reference list including English, French, and Spanish language references.
It is currently recommended that HIV-infected individuals with TB receive combined treatment for both diseases, irrespective of CD4+ cell count. ART (Anti Retroviral Therapy) along with ATT (Anti Tuberculosis Treatment) is the only available treatment in present time. Though the timing of starting ART is the debatable question due to the risk of immune reconstitution inflammatory syndrome (IRIS). The advantages of early ART include reduction in early mortality, reduction in relapses, preventing drug resistance to ATT and reduction in occurrence of HIV-associated infections other than TB. The disadvantages include cumulative toxicity of ART and ATT, drug interactions leading to inflammatory reactions are the limiting factors for choosing the combination of ATT and ART.
A systematic review investigated the optimal timing of starting antiretroviral therapy in adults with newly diagnosed pulmonary tuberculosis. The review authors included eight trials, that were generally well-conducted, with over 4500 patients in total. The early provision of antiretroviral therapy in HIV-infected adults with newly diagnosed tuberculosis improved survival in patients who had a low CD4 count (less than 0.050 x 109 cells/L). However, such therapy doubled the risk for IRIS. Regarding patients with higher CD4 counts (more than 0.050 x 109 cells/L), the evidence is not sufficient to make a conclusion about benefits or risks of early antiretroviral therapy.
Successful diagnosis of XDR-TB depends on the patient’s access to quality health-care services. If TB bacteria are found in the sputum, the diagnosis of TB can be made in a day or two, but this finding will not be able to distinguish between drug-susceptible and drug-resistant TB. To evaluate drug susceptibility, the bacteria need to be cultivated and tested in a suitable laboratory. Final diagnosis in this way for TB, and especially for XDR-TB, may take from 6 to 16 weeks. To reduce the time needed for diagnosis, new tools for rapid TB diagnosis are urgently needed.
The original method used to test for MDR-TB and XDR-TB was the Drug Susceptibility Testing (DST). DST is capable of determining how well four primary antitubercular drugs inhibit the growth of Mycobacterium Tuberculosis. The four primary antitubercular drugs are Isoniazid, Rifampin, Ethambutol and Pyrazinamide. Drug Susceptibility testing is done by making a Lowenstein-Jensen medium plate and spreading the bacteria on the plate. Disks containing one of the four primary drugs are added to the plate. After weeks of allowing the bacteria to grow the plate is checked for clear areas around the disk. If there is a clear area, the drug has killed the bacteria and most likely the bacteria is not resistant to that drug.
As "Mycobacterium tuberculosis" evolved new strains of resistant bacteria were being found such as XDR-TB. The problem was that primary DST was not suitable for testing bacteria strains that were extensively drug resistant. This problem was starting to be fixed when drug susceptibility tests started including not just the four primary drugs, but secondary drugs. This secondary test is known as Bactec MGIT 960 System. Although Bactec MGIT 960 System was accurate it was still slow at determining the level of resistance.
Diagnosis of MDR and XDR-TB in children is challenging. With an increasing number of cases being reported worldwide there is a great need for better diagnostic tools available for pediatric patients.
In recent years drug resistant tuberculosis testing has shown a lot of progress. Some studies have found an in-house assay that could rapidly detect resistance to drugs involved in the definition of XDR-TB directly from smear-positive specimens. The assay is called Reverse Line Blot Hybridization Assay also known as RLBH. The study showed that the results of RLBH were as accurate as other drug susceptibility tests, but at the same time didn`t take weeks to get results. RLBH testing only took 3 days to determine how resistant the strain of bacteria was.
The current research has shown progress in the testing of drug resistance. A recent study found that a research technique known as direct nitrate reductase assay (D-NRA) showed efficient accuracy for the rapid and simultaneous detection of resistance to isoniazid (INH), rifampicin (RIF), kanamycin (KAN) and ofloxacin (OFL). D-NRA results were obtained in 16.9 days, comparably less than other drug susceptibility testing. At the same time the study mentioned how D-NRA is a low-cost technology, easy to set up in clinical laboratories and suitable to be used for DST of M. tuberculosis in all smear-positive samples.
Diagnosis of TB meningitis is made by analysing cerebrospinal fluid collected by lumbar puncture. When collecting CSF for suspected TB meningitis, a minimum of 1ml of fluid should be taken (preferably 5 to 10ml). The CSF usually has a high protein, low glucose and a raised number of lymphocytes. Acid-fast bacilli are sometimes seen on a CSF smear, but more commonly, "M. tuberculosis" is grown in culture. A spiderweb clot in the collected CSF is characteristic of TB meningitis, but is a rare finding. ELISPOT testing is not useful for the diagnosis of acute TB meningitis and is often false negative, but may paradoxically become positive after treatment has started, which helps to confirm the diagnosis.