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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.
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.
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.
To make the diagnosis of a urinary tract infection in children, a positive urinary culture is required. Contamination poses a frequent challenge depending on the method of collection used, thus a cutoff of 10 CFU/mL is used for a "clean-catch" mid stream sample, 10 CFU/mL is used for catheter-obtained specimens, and 10 CFU/mL is used for suprapubic aspirations (a sample drawn directly from the bladder with a needle). The use of "urine bags" to collect samples is discouraged by the World Health Organization due to the high rate of contamination when cultured, and catheterization is preferred in those not toilet trained. Some, such as the American Academy of Pediatrics recommends renal ultrasound and voiding cystourethrogram (watching a person's urethra and urinary bladder with real time x-rays while they urinate) in all children less than two years old who have had a urinary tract infection. However, because there is a lack of effective treatment if problems are found, others such as the National Institute for Health and Care Excellence only recommends routine imaging in those less than six months old or who have unusual findings.
In straightforward cases, a diagnosis may be made and treatment given based on symptoms alone without further laboratory confirmation. In complicated or questionable cases, it may be useful to confirm the diagnosis via urinalysis, looking for the presence of urinary nitrites, white blood cells (leukocytes), or leukocyte esterase. Another test, urine microscopy, looks for the presence of red blood cells, white blood cells, or bacteria. Urine culture is deemed positive if it shows a bacterial colony count of greater than or equal to 10 colony-forming units per mL of a typical urinary tract organism. Antibiotic sensitivity can also be tested with these cultures, making them useful in the selection of antibiotic treatment. However, women with negative cultures may still improve with antibiotic treatment. As symptoms can be vague and without reliable tests for urinary tract infections, diagnosis can be difficult in the elderly.
Testing for bacteriuria is often performed in those with symptoms of a urinary tract infection. Testing is often done in other scenarios as in failure to thrive of a newborn or confusion in the elderly. Screening for bacteriuria is recommended in pregnancy as there is evidence that asymptomatic bacteriuria can lead to low birth weight and preterm delivery.
- Bacteriuria can be detected by urine dipstick test. The urinary nitrite test will be able to detect any nitrate-reducing bacteria in the urine. The leukocyte esterase test detects the presence of leukocytes (white blood cells) in the urine which can be associated with a urinary tract infection.The urine dipstick test is readily available and provides fast results.
- Microscopy can also be used to detect bacteriuria. It is more specific, especially when used with gram staining, but requires more time and equipment.
- The gold standard for detecting bacteriuria is a bacterial culture which identifies the actual organism. This test is more specific but can take several days to obtain a result. As a result, clinicians will often treat a bacteriuria based on the results of the urine dipstick test while waiting for the culture results. The culture will often provide antibiotic sensitivity.
Bacteriuria can be confirmed if a single bacterial species is isolated in a concentration greater than 100,000 colony forming units per millilitre of urine in clean-catch midstream urine specimens (one for men, two consecutive specimens with the same bacterium for women). For urine collected via bladder catheterization in men and women, a single urine specimen with greater than 100,000 colony forming units of a single species per millilitre is considered diagnostic. The threshold is also 100 colony forming units of a single species per millilitre for women displaying UTI symptoms.
Analysis of the urine may show signs of urinary tract infection. Specifically, the presence of nitrite and white blood cells on a urine test strip in patients with typical symptoms are sufficient for the diagnosis of pyelonephritis, and are an indication for empirical treatment. Blood tests such as a complete blood count may show neutrophilia. Microbiological culture of the urine, with or without blood cultures and antibiotic sensitivity testing are useful for establishing a formal diagnosis, and are considered mandatory.
The decision to treat bacteriuria depends on the presence of accompany symptoms and comorbidities.
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.
If a kidney stone is suspected (e.g. on the basis of characteristic colicky pain or the presence of a disproportionate amount of blood in the urine), a kidneys, ureters, and bladder x-ray (KUB film) may assist in identifying radioopaque stones. Where available, a noncontrast helical CT scan with 5 millimeter sections is the diagnostic modality of choice in the radiographic evaluation of suspected nephrolithiasis. All stones are detectable on CT scans except very rare stones composed of certain drug residues in the urine. In patients with recurrent ascending urinary tract infections, it may be necessary to exclude an anatomical abnormality, such as vesicoureteral reflux or polycystic kidney disease. Investigations used in this setting include kidney ultrasonography or voiding cystourethrography. CT scan or kidney ultrasonography is useful in the diagnosis of xanthogranulomatous pyelonephritis; serial imaging may be useful for differentiating this condition from kidney cancer.
Ultrasound findings that indicate pyelonephritis are enlargement of the kidney, edema in the renal sinus or parenchyma, bleeding, loss of corticomedullary differentiation, abscess formation, or an areas of poor blood flow on doppler ultrasound. However, ultrasound findings are seen in only 20% to 24% of people with pyelonephritis.
A DMSA scan is a radionuclide scan that uses dimercaptosuccinic acid in assessing the kidney morphology. It is now the most reliable test for the diagnosis of acute pyelonephritis.
Urogenital tuberculosis may cause strictures of the ureter, which, however, may heal when infection is treated.
It usually strikes young adults with tuberculosis in other places of the body as well. It is common in Asia, but less common in sub-Saharan Africa.
Urinary catheters should be inserted using aseptic technique and sterile equipment (including sterile gloves, drape, sponges, antiseptic and sterile solution), particularly in an acute care setting. Hands should be washed before and after catheter insertion. Overall, catheter use should be minimized in all patients, particularly those at higher risk of CAUTI and mortality (e.g. the elderly or those with impaired immunity).
TB is one of the most common infections in people living with HIV/AIDS. In places where XDR-TB is most common, people living with HIV are at greater risk of becoming infected with XDR-TB, compared with people without HIV, because of their weakened immunity. If there are a lot of HIV-infected people in these places, then there will be a strong link between XDR-TB and HIV. Fortunately, in most of the places with high rates of HIV, XDR-TB is not yet widespread. For this reason, the majority of people with HIV who develop TB will have drug-susceptible or ordinary TB, and can be treated with standard first-line anti-TB drugs. For those with HIV infection, treatment with antiretroviral drugs will likely reduce the risk of becoming infected with XDR-TB, just as it does with ordinary TB.
A research study titled "TB Prevalence Survey and Evaluation of Access to TB Care in HIV-Infected and Uninfected TB Patients in Asembo and Gem, Western Kenya", says that HIV/AIDS is fueling large increases in TB incidence in Africa, and a large proportion of cases are not diagnosed.
There are several ways that drug resistance to TB, and drug resistance in general, can be prevented:
1. Rapid diagnosis & treatment of TB: One of the greatest risk factors for drug resistant TB is problems in treatment and diagnosis, especially in developing countries. If TB is identified and treated soon, drug resistance can be avoided.
2. Completion of treatment: Previous treatment of TB is an indicator of MDR TB. If the patient does not complete his/her antibiotic treatment, or if the physician does not prescribe the proper antibiotic regimen, resistance can develop. Also, drugs that are of poor quality or less in quantity, especially in developing countries, contribute to MDR TB.
3. Patients with HIV/AIDS should be identified and diagnosed as soon as possible. They lack the immunity to fight the TB infection and are at great risk of developing drug resistance.
4. Identify contacts who could have contracted TB: i.e. family members, people in close contact, etc.
5. Research: Much research and funding is needed in the diagnosis, prevention and treatment of TB and MDR TB.
"Opponents of a universal tuberculosis treatment, reasoning from misguided notions of cost-effectiveness, fail to acknowledge that MDRTB is not a disease of poor people in distant places. The disease is infectious and airborne. Treating only one group of patients looks inexpensive in the short run, but will prove disastrous for all in the long run."- Paul Farmer
Bacteremia is most commonly diagnosed by blood culture, in which a sample of blood drawn from the vein by needle puncture is allowed to incubate with a medium that promotes bacterial growth. If bacteria are present in the bloodstream at the time the sample is obtained, the bacteria will multiply and can thereby be detected.
Any bacteria that incidentally find their way to the culture medium will also multiply. For example, if the skin is not adequately cleaned before needle puncture, contamination of the blood sample with normal bacteria that live on the surface of the skin can occur. For this reason, blood cultures must be drawn with great attention to sterile process. The presence of certain bacteria in the blood culture, such as S"taphylococcus aureus", "Streptococcus pneumoniae", and "Escherichia coli" almost never represent a contamination of the sample. On the other hand, contamination may be more highly suspected if organisms like "Staphylococcus epidermidis" or "Propionibacterium acnes" grow in the blood culture.
Two blood cultures drawn from separate sites of the body are often sufficient to diagnose bacteremia. Two out of two cultures growing the same type of bacteria usually represents a real bacteremia, particularly if the organism that grows is not a common contaminant. One out of two positive cultures will usually prompt a repeat set of blood cultures to be drawn to confirm whether a contaminant or a real bacteremia is present. The patient's skin is typically cleaned with an alcohol-based product prior to drawing blood to prevent contamination. Blood cultures may be repeated at intervals to determine if persistent — rather than transient — bacteremia is present.
Prior to drawing blood cultures, a thorough patient history should be taken with particular regard to presence of both fevers and chills, other focal signs of infection such as in the skin or soft tissue, a state of immunosuppression, or any recent invasive procedures.
Ultrasound of the heart is recommended in all those with bacteremia due to "Staphylococcus aureus" to rule out infectious endocarditis.
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%.
Due to the atypical presentation and rarity of the infection, it takes a physician longer to diagnose than more common types of bladder infections. Diagnosis requires a personalized investigation with consideration to risk factors and symptoms (Bobba). Radiology of the abdominal or pubic region has proven to be an important tool in reaching a definitive diagnosis of conditions causing gas in the urinary tract. Computer tomography, or CT scans, are of most help due to their high sensitivity in detecting gas and air bubbles (Gheonea, Bondari). However, radiology is normally not the first tool used to diagnose. Most diagnoses are made by chance after imaging examination (Weerakkody). Sometimes, even when patients don’t show symptoms, their Emphysematous cystitis infection level can be very advanced already (De Baets, Baert). Gas in the bladder wall will often have the appearance of cobblestone or a “beaded necklace” with the use of conventional radiography (Weerakkody). Delayed diagnosis can lead to a severe infection, extension of the uterus, rupturing of the bladder, and death. Emphysematous cystitis has an overall mortality rate of 7%. However, surgery is only considered in severe cases where the disease progresses involving the ureters, kidneys, or adrenal glands. When required, surgery may be extensive. (De Baets, Baert).
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.
Community-based treatment programs such as DOTS-Plus, a MDR-TB-specialized treatment using the popular Directly Observed Therapy – Short Course (DOTS) initiative, have shown considerable success in the of the world. In these locales, these programs have proven to be a good option for proper treatment of MDR-TB in poor, rural areas. A successful example has been in Lima, Peru, where the program has seen cure rates of over 80%.
However, TB clinicians have expressed concern in the DOTS program administered in the Republic of Georgia because it is anchored in a passive case finding. This means that the system depends on patients coming to health care providers, without conducting compulsory screenings. As medical anthropologists like Erin Koch have shown, this form of implementation does not suit all cultural structures. They urge that the DOTS protocol be constantly reformed in the context of local practices, forms of knowledge and everyday life.
Erin Koch has utilized Paul Farmer’s concept of “structural” violence as a perspective for understanding how “institutions, environment, poverty, and power reproduce, solidify, and naturalize the uneven distribution of disease and access to resources”. She has also studied the effectiveness of the DOTS protocol in the widespread disease of tuberculosis in the Georgian prison system. Unlike the DOTS passive case finding utilized for the general Georgian public, the multiple-level surveillance in the prison system has proven more successful in reducing the spread of tuberculosis while increasing rates of cure.
Koch critically notes that because the DOTS protocol aims to change the individual’s behavior without addressing the need to change the institutional, political, and economic contexts, certain limitations arise, such as MDR tuberculosis.
Paul Farmer believes that DOTS should be the cornerstone of tuberculosis control around the world.
For healthcare-associated bacteremia due to intravenous catheters, the IDSA has published guidelines for catheter removal. Short term catheters (in place 14 days) should be removed if the patient is developing signs or symptoms of sepsis or endocarditis, or if blood cultures remain positive for more than 72 hours.
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.