Tuberculosis is the top infectious disease worldwide, with an estimated 1.1 million new cases in children reported in 2018. While rates of tuberculosis remain low in the US, children are at high risk of developing disease if infected.
Dr. Rachel Orscheln joins the show to discuss global trends in TB, and appropriate screening strategies that can detect TB in those who are infected, and reduce false positives in those at low risk.
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Tuberculosis in Childhood
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Learn more about Rachel Orscheln, MD
Rachel Orscheln, MD
Rachel Orscheln, MD, is a Washington University pediatric infectious disease physician at St. Louis Children’s Hospital.Learn more about Rachel Orscheln, MD
Transcription:
Tuberculosis in Childhood
Melanie Cole, MS (Host): Tuberculosis is the top infectious disease worldwide with an estimated 1.1 million new cases in children reported in 2018. This is Radio Rounds with St. Louis Children’s Hospital. I'm Melanie Cole and today we’re discussing global trends in tuberculosis and appropriate screening strategies that can detect it in those who are effected. Joining me is Dr. Rachel Orscheln. She’s a Washington University pediatric infectious disease physician at St. Louis Children’s Hospital. Dr. Orscheln, it’s a please to have you join us again. Tell us a little bit about the global trends of pediatric tuberculosis, the U.S. trends, and even Missouri trends.
Rachel Orscheln MD (Guest): Overall fortunately we have seen a decline in the number of cases of tuberculosis over time. With that being said, we still do continue to see cases of children who test positive for tuberculosis disease and infection in the United States.
Host: So then let’s talk a little bit about the different between TB infection and active disease. Tell us a little bit about that and the risk of progression from latent to active disease.
Dr. Orscheln: So tuberculosis refers to any infection caused by mycobacterium tuberculosis. This infection can exist in a clinically asymptomatic state, which is referred to as latent tuberculosis, or with signs and symptoms of disease, which is referred to as tuberculosis disease. The most frequent form of tuberculosis disease is pulmonary infection, and this can present with cough, fever, weight loss, night sweats, and disease. Tuberculosis disease should be considered in patients with prolonged respiratory disease for which there is no other explanation, especially if they have risk factors for tuberculosis. In pediatrics, extrapulmonary tuberculosis—which means infection occurring outside of the lungs—can occur more frequently than it does in adults. The most frequent site of extrapulmonary infection with tuberculosis in pediatrics can include the lymph nodes, bones and joints, or central nervous system.
Individuals who are infected with tuberculosis and have an asymptomatic state have about a 10% lifetime risk of developing active tuberculosis. Individuals who are at highest risk of developing active tuberculosis are those who are recently infected—so within the first two years of acquisition of the mycobacterium tuberculosis. Additionally people who are very young and those who have underlying medical conditions such as immunocompromising conditions are at increased risk of developing active tuberculosis disease.
Host: So then Dr. Orscheln, when should children and adolescents be screened for infection and disease?
Dr. Orscheln: Well, it’s certainly important to screen anyone who’s had a recent known exposure, but that’s a relatively uncommon occurrence. Generally speaking, children should be screened by their primary care providers for tuberculosis and really all children should be screened. Now, this doesn’t always involve skin testing or a blood test, but a simple series of questions that can assess a risk for tuberculosis infection. Some of the questions that are included in screening for tuberculosis can include was the child born outside of the United States or has the child travelled outside of the United States specifically to Africa, Asia, Latin America, or Eastern Europe for greater than a week. Has the child had any exposure to anyone with tuberculosis or has the child had close contact with persons who have had a positive skin test for tuberculosis or other risk factors for tuberculosis or other risk factors for tuberculosis. These would include incarceration, illegal drug use, HIV infection, or travel to or origin from high risk regions outside of the United States.
Host: So additionally with the screening and if you know that the child has some of those risk factors, are there some warning signs for the pediatricians if the parent brings in a child and tells these things. Are there some other warning signs? The clinical presentation. Tell us about that.
Dr. Orscheln: Children who have positive testing on the screening questionnaire should then receive skin testing or gamma interferon release assay testing for tuberculosis. Skin testing is generally preferred for children who are less than two years of age, and either skin testing or gamma interferon release assay testing can be performed on children who are greater than two years of age.
Host: Well then why do so many cases go undiagnosed? Certainly there's got to be a diagnostic gold standard for active TB. Tell us a little bit about why.
Dr. Orscheln: Well, the clinical presentation of tuberculosis generally is primarily a pulmonary presentation, but this can be subtle in children and difficult to distinguish from other illnesses that present with respiratory symptoms. Children with tuberculosis can present with fever, respiratory symptoms—especially those that are prolonged and progressive—and weight loss or failure to grow properly. The diagnosis of pulmonary tuberculosis is relatively uncommon in the United States but should be suspected especially in children with risk factors for tuberculosis.
Host: Are pediatric tuberculosis deaths underreported?
Dr. Orscheln: Outside of the United States resource limitation may be one of the main reasons why tuberculosis goes undiagnosed in childhood. Additionally, however, pediatric tuberculosis can have overlap with other more common clinical syndromes in children such as acute bacterial pneumonia or viral respiratory tract infections. Additionally children with pulmonary tuberculosis have a different clinical phenotypes than adults with pulmonary tuberculosis. In medical school we’re taught that tuberculosis often presents with a cavitary pulmonary disease. In pediatrics, this is relatively uncommon. Adolescents and young adults may present with this particular clinical finding, but children because it’s their primary infection as opposed to reactivation disease often do not have cavitary pulmonary disease. For this reason as well they often have fewer mycobacterial organisms in their pulmonary disease and thus we have a greater difficulty of finding that bacteria and thus making the diagnosis of tuberculosis.
Children often don’t generate the same force of cough. So they are often unable to produce the bacteria in their sputum so that we can make the diagnosis. So we have to rely on other routes such as gastric aspirates that look for bacteria that have been swallowed by the child after coughing. Compared to adults, children are often described as having paucibacillary disease, which means they have fewer organisms. This has the benefit that they are often less infectious than adults. We often consider that children less than 12 years of age are not infectious for tuberculosis. We do isolate children who we suspect of having pulmonary tuberculosis, but often this is so we can evaluate the caregivers around them who may have infected them and thus be infectious to other individuals in the hospital setting. Worldwide it is estimated that there are more pediatric tuberculosis deaths than are reported. This may be because the deaths are attributed to other causes such as HIV infection or malnutrition and that the diagnostic testing is lacking in other places in the world where tuberculosis is more common.
Host: So then speak about treatments for other providers that may recognize this. What do you do for it?
Dr. Orscheln: It children who are diagnosed with latent tuberculosis, there are several different regiments that can be given over time to prevent active pulmonary disease. In fact, children can reduce their risk nearly to zero of developing active pulmonary disease by being treated for latent tuberculosis. The two most common regiments that are used for treating latent tuberculosis include the administration of isoniazid for a nine month course that is generally given daily and is extremely well tolerated. A newer regiment that has recently been described includes the use of isoniazid and an additional drug called rifapentine. Both are delivered on a once a week basis for 12 weeks. This is a greatly reduced number of doses and is equally as well tolerated as isoniazid, but the course is completed in a much shorter time frame.
For patients with active pulmonary tuberculosis or active disease at any site, consultation with a pediatric disease specialist would be warranted. Treatment in those particular circumstances is tailored to the susceptibility profile of the organism, if that is known. Generally speaking treatment is initiated with four drugs and then potentially decreased to two or three drugs for the completion of the course.
Host: So when would you advise a pediatrician to refer to a specialist? Before we wrap up, what else do you want other providers to know about tuberculosis and what you're seeing as far as the trends in this disease.
Dr. Orscheln: Pediatricians or other healthcare providers can feel free to refer their patients to a pediatric infectious disease specialist if they have any concerns about the diagnosis of tuberculosis. Additionally, if they are uncomfortable latent tuberculosis we often see those patients in our clinic to determine what is the best regiment and follow up of patients with latent tuberculosis.
Host: Thank you so much Dr. Orscheln for joining us today and sharing your expertise. Such an interesting topic. That concludes this episode of Radio Rounds with St. Louis Children’s Hospital. To consult with a specialist or to learn more about services and resources available at St. Louis Children’s Hospital, please call the children’s direct physician access line at 1-800-678-HELP. You can also visit our website at stlouischildrens.org for more information and to get connected with one of our providers. Please remember to subscribe, rate, and review this podcast and all the other St. Louis Children’s Hospital podcasts. I'm Melanie Cole.
Tuberculosis in Childhood
Melanie Cole, MS (Host): Tuberculosis is the top infectious disease worldwide with an estimated 1.1 million new cases in children reported in 2018. This is Radio Rounds with St. Louis Children’s Hospital. I'm Melanie Cole and today we’re discussing global trends in tuberculosis and appropriate screening strategies that can detect it in those who are effected. Joining me is Dr. Rachel Orscheln. She’s a Washington University pediatric infectious disease physician at St. Louis Children’s Hospital. Dr. Orscheln, it’s a please to have you join us again. Tell us a little bit about the global trends of pediatric tuberculosis, the U.S. trends, and even Missouri trends.
Rachel Orscheln MD (Guest): Overall fortunately we have seen a decline in the number of cases of tuberculosis over time. With that being said, we still do continue to see cases of children who test positive for tuberculosis disease and infection in the United States.
Host: So then let’s talk a little bit about the different between TB infection and active disease. Tell us a little bit about that and the risk of progression from latent to active disease.
Dr. Orscheln: So tuberculosis refers to any infection caused by mycobacterium tuberculosis. This infection can exist in a clinically asymptomatic state, which is referred to as latent tuberculosis, or with signs and symptoms of disease, which is referred to as tuberculosis disease. The most frequent form of tuberculosis disease is pulmonary infection, and this can present with cough, fever, weight loss, night sweats, and disease. Tuberculosis disease should be considered in patients with prolonged respiratory disease for which there is no other explanation, especially if they have risk factors for tuberculosis. In pediatrics, extrapulmonary tuberculosis—which means infection occurring outside of the lungs—can occur more frequently than it does in adults. The most frequent site of extrapulmonary infection with tuberculosis in pediatrics can include the lymph nodes, bones and joints, or central nervous system.
Individuals who are infected with tuberculosis and have an asymptomatic state have about a 10% lifetime risk of developing active tuberculosis. Individuals who are at highest risk of developing active tuberculosis are those who are recently infected—so within the first two years of acquisition of the mycobacterium tuberculosis. Additionally people who are very young and those who have underlying medical conditions such as immunocompromising conditions are at increased risk of developing active tuberculosis disease.
Host: So then Dr. Orscheln, when should children and adolescents be screened for infection and disease?
Dr. Orscheln: Well, it’s certainly important to screen anyone who’s had a recent known exposure, but that’s a relatively uncommon occurrence. Generally speaking, children should be screened by their primary care providers for tuberculosis and really all children should be screened. Now, this doesn’t always involve skin testing or a blood test, but a simple series of questions that can assess a risk for tuberculosis infection. Some of the questions that are included in screening for tuberculosis can include was the child born outside of the United States or has the child travelled outside of the United States specifically to Africa, Asia, Latin America, or Eastern Europe for greater than a week. Has the child had any exposure to anyone with tuberculosis or has the child had close contact with persons who have had a positive skin test for tuberculosis or other risk factors for tuberculosis or other risk factors for tuberculosis. These would include incarceration, illegal drug use, HIV infection, or travel to or origin from high risk regions outside of the United States.
Host: So additionally with the screening and if you know that the child has some of those risk factors, are there some warning signs for the pediatricians if the parent brings in a child and tells these things. Are there some other warning signs? The clinical presentation. Tell us about that.
Dr. Orscheln: Children who have positive testing on the screening questionnaire should then receive skin testing or gamma interferon release assay testing for tuberculosis. Skin testing is generally preferred for children who are less than two years of age, and either skin testing or gamma interferon release assay testing can be performed on children who are greater than two years of age.
Host: Well then why do so many cases go undiagnosed? Certainly there's got to be a diagnostic gold standard for active TB. Tell us a little bit about why.
Dr. Orscheln: Well, the clinical presentation of tuberculosis generally is primarily a pulmonary presentation, but this can be subtle in children and difficult to distinguish from other illnesses that present with respiratory symptoms. Children with tuberculosis can present with fever, respiratory symptoms—especially those that are prolonged and progressive—and weight loss or failure to grow properly. The diagnosis of pulmonary tuberculosis is relatively uncommon in the United States but should be suspected especially in children with risk factors for tuberculosis.
Host: Are pediatric tuberculosis deaths underreported?
Dr. Orscheln: Outside of the United States resource limitation may be one of the main reasons why tuberculosis goes undiagnosed in childhood. Additionally, however, pediatric tuberculosis can have overlap with other more common clinical syndromes in children such as acute bacterial pneumonia or viral respiratory tract infections. Additionally children with pulmonary tuberculosis have a different clinical phenotypes than adults with pulmonary tuberculosis. In medical school we’re taught that tuberculosis often presents with a cavitary pulmonary disease. In pediatrics, this is relatively uncommon. Adolescents and young adults may present with this particular clinical finding, but children because it’s their primary infection as opposed to reactivation disease often do not have cavitary pulmonary disease. For this reason as well they often have fewer mycobacterial organisms in their pulmonary disease and thus we have a greater difficulty of finding that bacteria and thus making the diagnosis of tuberculosis.
Children often don’t generate the same force of cough. So they are often unable to produce the bacteria in their sputum so that we can make the diagnosis. So we have to rely on other routes such as gastric aspirates that look for bacteria that have been swallowed by the child after coughing. Compared to adults, children are often described as having paucibacillary disease, which means they have fewer organisms. This has the benefit that they are often less infectious than adults. We often consider that children less than 12 years of age are not infectious for tuberculosis. We do isolate children who we suspect of having pulmonary tuberculosis, but often this is so we can evaluate the caregivers around them who may have infected them and thus be infectious to other individuals in the hospital setting. Worldwide it is estimated that there are more pediatric tuberculosis deaths than are reported. This may be because the deaths are attributed to other causes such as HIV infection or malnutrition and that the diagnostic testing is lacking in other places in the world where tuberculosis is more common.
Host: So then speak about treatments for other providers that may recognize this. What do you do for it?
Dr. Orscheln: It children who are diagnosed with latent tuberculosis, there are several different regiments that can be given over time to prevent active pulmonary disease. In fact, children can reduce their risk nearly to zero of developing active pulmonary disease by being treated for latent tuberculosis. The two most common regiments that are used for treating latent tuberculosis include the administration of isoniazid for a nine month course that is generally given daily and is extremely well tolerated. A newer regiment that has recently been described includes the use of isoniazid and an additional drug called rifapentine. Both are delivered on a once a week basis for 12 weeks. This is a greatly reduced number of doses and is equally as well tolerated as isoniazid, but the course is completed in a much shorter time frame.
For patients with active pulmonary tuberculosis or active disease at any site, consultation with a pediatric disease specialist would be warranted. Treatment in those particular circumstances is tailored to the susceptibility profile of the organism, if that is known. Generally speaking treatment is initiated with four drugs and then potentially decreased to two or three drugs for the completion of the course.
Host: So when would you advise a pediatrician to refer to a specialist? Before we wrap up, what else do you want other providers to know about tuberculosis and what you're seeing as far as the trends in this disease.
Dr. Orscheln: Pediatricians or other healthcare providers can feel free to refer their patients to a pediatric infectious disease specialist if they have any concerns about the diagnosis of tuberculosis. Additionally, if they are uncomfortable latent tuberculosis we often see those patients in our clinic to determine what is the best regiment and follow up of patients with latent tuberculosis.
Host: Thank you so much Dr. Orscheln for joining us today and sharing your expertise. Such an interesting topic. That concludes this episode of Radio Rounds with St. Louis Children’s Hospital. To consult with a specialist or to learn more about services and resources available at St. Louis Children’s Hospital, please call the children’s direct physician access line at 1-800-678-HELP. You can also visit our website at stlouischildrens.org for more information and to get connected with one of our providers. Please remember to subscribe, rate, and review this podcast and all the other St. Louis Children’s Hospital podcasts. I'm Melanie Cole.