Project Description

CNS Tuberculosis Fast Facts

Central nervous system (CNS) CNS tuberculosis is a brain infection caused by a bacteria called Mycobacterium tuberculosis.

The tuberculosis bacteria commonly infect the lungs, but the infection may migrate to other parts of the body, including the brain and spinal cord.

Having a compromised immune system can put you at risk of developing a life-threatening CNS tuberculosis infection. People with HIV/AIDS or other conditions that affect the immune system and those using immune-suppressant drugs are at increased risk.

People with HIV are about five times more likely than HIV-negative people to experience central nervous system involvement when they have a tuberculosis infection.

Sometimes the tuberculosis bacterium does not cause illness and remains dormant in the body, a condition known as a latent infection. As many as 13 million people in the United States are estimated to have a latent tuberculosis infection.

United Brain Association

As many as 13 million people in the United States are estimated to have a latent tuberculosis infection.

What is CNS Tuberculosis?

Central nervous system (CNS) tuberculosis is an infection of the brain or spinal cord caused by a bacteria called Mycobacterium tuberculosis. Tuberculosis infections (TB) are common in developing countries, but they are also increasingly common in developed countries such as the United States.

Tuberculosis infections often begin in the lungs and migrate to the brain and other parts of the central nervous system (CNS). In the CNS, the infection can cause brain lesions, meningitis, hydrocephalus, or brain abscesses.

An estimated 10% of people with a TB infection experience CNS tuberculosis. However, the risk of CNS involvement is much higher in people with compromised immune systems, such as people with HIV or who have undergone an organ transplant.

Symptoms of CNS Tuberculosis

Symptoms of the condition can include:

  • Headache
  • Fever and/or chills
  • Nausea and vomiting
  • Sleepiness, fatigue, or loss of consciousness
  • Seizures
  • Weakness or paralysis on one side of the body

What Causes CNS Tuberculosis?

A tuberculosis infection begins when a person breathes the bacteria into their lungs. It is easily passed from person to person through the air. The infection most often causes symptoms in the lungs, but it may travel to the central nervous system, where it can have a severe impact.

The tuberculosis bacteria can infect anyone and cause serious illness. However, people with compromised immune systems are at increased risk of TB infections that spread to the brain or spinal column and cause additional life-threatening complications. 

People at increased risk include:

  • People with HIV/AIDS
  • People who have had an organ transplant
  • People taking immune-suppressive medications to treat autoimmune disorders such as rheumatoid arthritis

Is CNS Tuberculosis Hereditary?

External environmental sources cause CNS tuberculosis, and family history plays no part in developing an infection.

How Is CNS Tuberculosis Detected?

Early detection of CNS tuberculosis is essential because potentially life-threatening complications are more likely to occur if treatment is delayed until symptoms are advanced. Unfortunately, early diagnosis of the condition is difficult because the first symptoms are usually vague and may be caused by various problems other than an infection.

Because the infection usually affects the lungs first, respiratory symptoms are common. These symptoms may include:

  • Cough
  • Chest pain
  • Coughing up blood or phlegm
  • Fever and chills
  • Weakness
  • Fatigue
  • Loss of appetite
  • Night sweating

If the infection is left untreated, more severe symptoms may develop. Eventually, an untreated infection is likely to be fatal.

How Is CNS Tuberculosis Diagnosed?

When your doctor suspects CNS tuberculosis may be present, they may follow a diagnostic procedure that includes:

  • Medical history questions. Your doctor will look for signs that you may be at increased risk for TB infection.
  • Blood tests. These laboratory tests will look for signs of infection in your bloodstream.
  • Chest x-rays to look for infection in the lungs.
  • Lumbar puncture (spinal tap). This test will look for evidence of the fungus in the cerebral spinal fluid (CSF).
  • Imaging tests. Magnetic resonance imaging (MRI) and computerized tomography (CT) scans can be used to produce an image of your brain. An infection is likely to show up on these scans.

How Is CNS Tuberculosis Treated?

Treatment of CNS tuberculosis involves drugs to eliminate the infection source and prevent relapses.

  • Antibiotic medications such as isoniazid, rifampicin, and pyrazinamide are typically used to treat the infection.
  • Corticosteroids may be used to relieve symptoms associated with meningitis caused by CNS tuberculosis. However, this treatment is the subject of some controversy among doctors.
  • Lumbar punctures or other procedures to relieve pressure in the brain may be required if the infection causes a buildup of cerebrospinal fluid.
  • Anti-seizure medications may be used to treat or prevent seizures.
  • Maintenance treatment with antibiotic medications will usually continue for at least a year to prevent relapses.

How Does CNS Tuberculosis Progress?

Treatment of TB infections is usually successful, but the condition is often fatal when left untreated. Some strains of the tuberculosis bacteria are resistant to commonly used drugs, making the infection more difficult to treat and more likely to be fatal.

CNS tuberculosis in immune-compromised patients is more likely to be fatal. Some studies show a mortality rate as high as 65% among HIV patients, and organ-transplant patients have a mortality rate of up to 40%.

How Is CNS Tuberculosis Prevented?

Because TB infections are easily spread from person to person, preventing transmission is essential. Early identification of the infection is also crucial.

Preventive measures include:

  • Avoid crowded, enclosed spaces in locations where TB infections are known to exist.
  • Get tested for TB exposure after being in contact with TB patients.

People at increased risk of TB illness should consult a doctor about possible preventive treatments. High-risk groups include:

  • People with HIV
  • People with prior TB infections
  • Children
  • The elderly
  • IV drug users
  • People with diseases that weaken the immune system

CNS Tuberculosis Caregiver Tips

If you are a caregiver for a loved one with CNS tuberculosis, keep these tips in mind:

  • Attend doctor appointments with your loved one to understand the diagnosis, the treatment plan, and the expectations for recovery.
  • During recovery, provide a comfortable space for the sufferer free from noise, excessive stimulation, and stress.
  • After treatment, work with your loved one’s medical providers to learn how you can best support them as they recuperate. Understand the goals of any long-term therapies, and be realistic about expectations.
  • Call upon family and community to help out whenever possible. Don’t try to take sole responsibility for caregiving.

CNS Tuberculosis Brain Science

When it enters the central nervous system, tuberculosis can have a variety of effects, including:

  • The fungus can infect the meninges, thin membranes surrounding the brain and spinal cord. This infection is called meningitis, and it can produce life-threatening complications.
  • Tuberculosis bacteria may form tumor-like lumps called tuberculomas. These masses can put pressure on surrounding brain tissue and cause neurological symptoms.
  • Sometimes tuberculosis infections in the brain cause the development of pus-filled pockets called abscesses. Like tuberculomas, these abscesses may also exert pressure on brain tissue and cause symptoms, but abscesses are less common than tuberculomas.
  • The infection can trigger a buildup of cerebrospinal fluid (CSF), resulting in a condition called hydrocephalus. This condition also may put pressure on brain tissue and cause symptoms.

CNS Tuberculosis Research

Title: Economic Incentives and vDOT for Latent Tuberculosis Infection

Stage: Recruiting

Principal Investigator: Maunank Shah, MD, PhD

Johns Hopkins University

Baltimore, MD

Identifying and treating individuals with latent tuberculosis (TB) (LTBI) is a key strategy to achieving the goal of TB elimination in the US, but there are many challenges to reaching this goal. In Baltimore, where this research will be conducted, prior studies suggest 35% of non-US-born individuals may have latent TB. Individuals experiencing homelessness have also been found to be at higher risk for TB infection. However, socioeconomic factors such as poverty, access to care, health literacy, and language or cultural barriers present obstacles to treatment. Treatment for latent TB is rarely a priority for patients with many other competing needs. The length of treatment spans many months, and preliminary data shows that less than half will complete the prescribed treatment. To date, there are limited interventions shown to be effective in increasing adherence to LTBI therapy. Directly observed therapy (DOT) administered via video (Video-DOT, with case-management) has been shown to be effective at monitoring treatment in active TB, but there is limited data when applied to LTBI. Interventions that provide incentives to patients when they meet required therapeutic goals have been demonstrated extraordinarily effective in promoting therapeutic behavior change in diverse populations.

The goal of this randomized trial is to evaluate two adherence interventions ( Video DOT or Video DOT plus financial incentives) versus Usual Care to promote completion of treatment for latent TB among those found eligible and are prescribed short-course therapy (isoniazid+Rifampin(3HR), Isoniazid+rifapentine(3HP), or rifampin alone(4R)) for LTBI care.

The primary assessment of adherence will be treatment completion which is defined as taking 80% of the prescribed doses of medication, as determined by Medication Event Monitoring System (MEMS) caps (i.e., 10 of 12 doses for participants prescribed weekly doses of rifapentine and isoniazid; 96 of 120 doses for participants prescribed daily doses of rifampin; 67 of 84 doses of daily isoniazid and rifampin.

Video directly observed therapy (video-DOT) will use the Electronic Mobile Comprehensive Health Application (emocha) platform. This system provides a HIPAA-compliant approach for remote DOT combined with data collection that optimizes TB case management. The Video DOT system is comprised of a smartphone/tablet application used by patients and a web-based dashboard used by the TB clinic. The patient-side application (app) reminds patients to take their medications on a schedule specified by the clinician. For those randomized to the Video-DOT plus incentives arm, additional financial incentives (provided in real-time) are delivered contingent on verification of medication ingestion by video observation.

 

Title: Training Protocol on the Natural History of Tuberculosis

Stage: Recruiting

Principal Investigator: Steven M Holland, MD

National Institute of Allergy and Infectious Diseases (NIAID)

Bethesda, MD  

Mycobacterium tuberculosis (MTB) is a slow-growing bacterium that establishes latent infection in millions of persons worldwide but only leads to disease in 10% or less of these individuals. It typically causes pneumonia. However, dissemination to almost any other organ is possible. Drug resistance of the organism, co-infection with HIV, and paradoxical reactions upon treatment are all factors that may complicate treatment.

Host defense against mycobacterial infections is important. Specific defects within the innate immune system lead to Mendelian susceptibility to mycobacterial infections. HIV-infected individuals and persons treated with anti-tumor necrosis factor antibodies are highly susceptible to tuberculosis (TB) infection. Genetic influence on susceptibility to TB disease is complex and does not seem to be confined to a single gene or pathway.

Advancement in molecular techniques has expanded our understanding of the pathogenesis and epidemiology of MTB. Identification of gene mutations that confer antibiotic resistance is being exploited as an alternative to conventional drug susceptibility testing.

The natural history of all forms of TB disease (including co-infection with HIV and other infections) will be followed, and MTB isolates and blood from 100 infected patients will be obtained to study organism virulence and host immune function and genetic/epigenetic factors. While it is recognized that the number of TB cases that occur in the Washington, DC area and nationally is low, a mechanism must be in place to evaluate and treat these patients at the NIH Clinical Center. This protocol will also allow NIH infectious diseases trainees to manage challenging cases of TB.

 

Title: Azacytidine During Anti-tuberculosis Therapy (AZA)

Stage: Not Yet Recruiting

Principal Investigator: Andrew DiNardo

Baylor College of Medicine

Houston, TX

Tuberculosis has been shown to make immune genes inaccessible and slow immune response. The purpose of this research is to see if azacitidine is safe and can return the ability of the body to resist tuberculosis (TB), a contagious infection that attacks the lungs. Individuals with tuberculosis are being asked to participate. Some will receive a drug to restore a host immunity, while others can choose to receive standard of care. All patients will continue to receive standard of care tuberculosis therapy regardless of whether they choose to participate in the study.

This study is a Phase Ib/IIa single-institution, open-label, non-randomized clinical trial of subcutaneous azacitidine in pulmonary TB patients during the continuation phase of ATT.

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