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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.
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.
Diagnosis is made by history and examination.
In immunocompromised patients, pus is present in the urine but often no organism can be cultured. In children, polymerase chain reaction sequencing of urine can detect fragments of the infectious agent.
The procedure differs somewhat for women and men. Laboratory testing of urine samples now can be performed with dipsticks that indicate immune system responses to infection, as well as with microscopic analysis of samples. Normal human urine is sterile. The presence of bacteria or pus in the urine usually indicates infection. The presence of hematuria, or blood in the urine, may indicate acute UTIs, kidney disease, kidney stones, inflammation of the prostate (in men), endometriosis (in women), or cancer of the urinary tract. In some cases, blood in the urine results from athletic training, particularly in runners.
The American Urological Association recommends ongoing monitoring of children with VUR until the abnormality resolves or is no longer clinically significant. The recommendations are for annual evaluation of blood pressure, height, weight, analysis of the urine, and kidney ultrasound.
The younger the patient and the lower the grade at presentation the higher the chance of spontaneous resolution. Approximately 85% of grade I & II VUR cases will resolve spontaneously. Approximately 50% of grade III cases and a lower percentage of higher grades will also resolve spontaneously.
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.
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.
Since it is a rare disease, it remains a diagnosis of exclusion of other conditions with similar symptoms. The diagnosis is supported by the results of imaging studies such as computed tomography or magnetic resonance imaging, ultrasound of the abdomen (with or without doppler imaging) or intravenous urography.
Specialist vascular ultrasonographers should routinely look for left ovarian vein reflux in patients with lower limb varices especially if not associated with long or short saphenous reflux. The clinical pattern of varices differs between the two types of lower limb varices.
CT scanning is used to exclude abdominal or pelvic pathology. CT-Angiography/Venography can often demonstrate left ovarian vein reflux and image an enlarged left ovarian vein but is less sensitive and much more expensive than duplex Doppler ultrasound examination. Ultrasound requires that the ultrasonographer be experienced in venous vascular ultrasound and so is not always readily available. A second specialist ultrasound exam remains preferable to a CT scan.
As a wide range of pelvic and abdominal pathology can cause symptoms consistent with those symptoms due to left ovarian vein reflux, prior to embolisation of the left ovarian vein, a careful search for such diagnoses is essential. Consultation with general surgeons, gynaecologists, and possibly CT scanning should always be considered.
Urogenital tuberculosis may cause strictures of the ureter, which, however, may heal when infection is treated.
Diagnosis is based on results of bladder catheterization, ultrasonography, CT scan, cystourethroscopy, or pyelography, depending on the level of obstruction.
Unfortunately mesna is ineffective as a treatment once hemorrhagic cystitis has developed. Although rare, once a case of radiation-induced hemorrhagic cystitis is diagnosed there is no empirically-proven treatments to heal this type of condition, which can severely degrade a patient's quality of life and might possibly lead to renal failure with risk of death.
Viral hemorrhagic cystitis in children generally spontaneously resolves within a few days.
The first step in the treatment of HC should be directed toward clot evacuation. Bladder outlet obstruction from clots can lead to urosepsis, bladder rupture, and renal failure. Clot evacuation can be performed by placing a wide-lumen bladder catheter at bedside. The bladder can be irrigated with water or sodium chloride solution. The use of water is preferable because water can help with clot lysis. Care must be taken to not overdistend the bladder and cause a perforation.. Hyperbaric oxygen (HBO2) therapy has been proven to be effective in treating radiation-induced hemorrhagic cystitis.
Duplicated ureter is the most common renal abnormality, occurring in approximately 1% of the population.
Race: Duplicated ureter is more common in Caucasians than in African-Americans.
Sex: Duplicated ureter is more common in females. However, this may be due to the higher frequency of urinary tract infections in females, leading to a higher rate of diagnosis of duplicated ureter.
If left untreated, complications may arise including abscess formation, peritonitis, sepsis, and damage to the urinary tract by fibrosis and granuloma formation. It is recommended, as a first step, to drain the lesion with ultrasound or CT guidance. If a patient has an underlying obstructive problem it needs to be addressed according to its cause.
Laboratory investigations typically carried out include:
- microscopic examination of the urine, which may show red blood cells, bacteria, leukocytes, urinary casts and crystals;
- urine culture to identify any infecting organisms present in the urinary tract and sensitivity to determine the susceptibility of these organisms to specific antibiotics;
- complete blood count, looking for neutrophilia (increased neutrophil granulocyte count) suggestive of bacterial infection, as seen in the setting of struvite stones;
- renal function tests to look for abnormally high blood calcium blood levels (hypercalcemia);
- 24 hour urine collection to measure total daily urinary volume, magnesium, sodium, uric acid, calcium, citrate, oxalate and phosphate;
- collection of stones (by urinating through a StoneScreen kidney stone collection cup or a simple tea strainer) is useful. Chemical analysis of collected stones can establish their composition, which in turn can help to guide future preventive and therapeutic management.
In people with a history of stones, those who are less than 50 years of age and are presenting with the symptoms of stones without any concerning signs do not require helical CT scan imaging. A CT scan is also not typically recommended in children.
Otherwise a noncontrast helical CT scan with 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, such as from indinavir. Calcium-containing stones are relatively radiodense, and they can often be detected by a traditional radiograph of the abdomen that includes the kidneys, ureters, and bladder (KUB film). Some 60% of all renal stones are radiopaque. In general, calcium phosphate stones have the greatest density, followed by calcium oxalate and magnesium ammonium phosphate stones. Cystine calculi are only faintly radiodense, while uric acid stones are usually entirely radiolucent.
Where a CT scan is unavailable, an intravenous pyelogram may be performed to help confirm the diagnosis of urolithiasis. This involves intravenous injection of a contrast agent followed by a KUB film. Uroliths present in the kidneys, ureters or bladder may be better defined by the use of this contrast agent. Stones can also be detected by a retrograde pyelogram, where a similar contrast agent is injected directly into the distal ostium of the ureter (where the ureter terminates as it enters the bladder).
Renal ultrasonography can sometimes be useful, as it gives details about the presence of hydronephrosis, suggesting the stone is blocking the outflow of urine. Radiolucent stones, which do not appear on KUB, may show up on ultrasound imaging studies. Other advantages of renal ultrasonography include its low cost and absence of radiation exposure. Ultrasound imaging is useful for detecting stones in situations where X-rays or CT scans are discouraged, such as in children or pregnant women. Despite these advantages, renal ultrasonography in 2009 was not considered a substitute for noncontrast helical CT scan in the initial diagnostic evaluation of urolithiasis. The main reason for this is that compared with CT, renal ultrasonography more often fails to detect small stones (especially ureteral stones), as well as other serious disorders that could be causing the symptoms. A 2014 study confirmed that ultrasonography rather than CT as an initial diagnostic test results in less radiation exposure and did not find any significant complications.
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.
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%.
Diagnosis may include a fluorescence in situ hybridization (FISH) test, computed tomography urography (CTU), magnetic resonance urography (MRU), intravenous pyelography (IVP) x-ray, ureteroscopy, or biopsy.
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.
Prenatally diagnosed hydronephrosis (fluid-filled kidneys) suggest post-natal follow-up examination.
The strongest neo-natal presentation is urinary tract infection. A hydronephrotic kidney may present as a palpable abdominal mass in the newborn, and may suggest an ectopic ureter or ureterocele.
In older children, ureteral duplication may present as:
- Urinary tract infection - most commonly due to vesicoureteral reflux (flow of urine from the bladder into the ureter, rather than vice versa).
- Urinary incontinence in females occurs in cases of ectopic ureter entering the vagina, urethra or vestibule.
Treatment, depending on cause, may require prompt drainage of the bladder via catheterization, medical instrumentation, surgery (e.g., endoscopy, lithotripsy), hormonal therapy, or a combination of these modalities.
Treatment of the obstruction at the level of the ureter:
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.
Treatment consists of painkillers and surgical ablation of the dilated vein. This can be accomplished with open abdominal surgery (laparotomy) or keyhole surgery (laparoscopy). Recently, the first robot-assisted surgery was described.
Another approach to treatment involves catheter-based embolisation, often preceded by phlebography to visualise the vein on X-ray fluoroscopy.
Ovarian vein coil embolisation is an effective and safe treatment for pelvic congestion syndrome and lower limb varices of pelvic origin. Many patients with lower limb varices of pelvic origin respond to local treatment i.e. ultrasound guided sclerotherapy. In those cases, ovarian vein coil embolisation should be considered second line treatment to be used if veins recur in a short time period i.e. 1–3 years. This approach allows further pregnancies to proceed if desired. Coil embolisation is not appropriate if a future pregnancy is possible. This treatment has largely superseded operative options.
Coil embolisation requires exclusion of other pelvic pathology, expertise in endovascular surgery, correct placement of appropriate sized coils in the pelvis and also in the upper left ovarian vein, careful pre- and post-procedure specialist vascular ultrasound imaging, a full discussion of the procedure with the patient i.e. informed consent. Complications, such as coil migration, are rare but reported. Their sequelae are usually minor.
If a Nutcracker compression (see below) is discovered, stenting of the renal vein should be considered before embolization of the ovarian vein. Reducing outflow obstruction should always be the main objective.
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.