confirmatory test for tuberculosis :: Article CreatorWhat Is The Incubation Period Of Tuberculosis?
Tuberculosis (TB) is a contagious disease that can be very serious if not treated. TB can stay dormant in your body for decades, but it's contagious only when you have active symptoms.
Tuberculosis (TB) is spread through the air from one person to another and usually causes respiratory symptoms similar to the flu or pneumonia.
You can have it in your body before developing symptoms, which is known as dormant (latent) TB. When symptoms develop, it is considered active TB.
While TB can be dormant for many years, it usually only becomes active within 2 years of the initial infection.
The incubation period for developing active tuberculosis ranges from several weeks to 2 years. This timeline can be important in considering global health resources.
Read on to learn more about the incubation period for tuberculosis.
If you're going to develop active tuberculosis, it's most likely to cause symptoms shortly after you've been exposed. According to a 2018 review, the average incubation period ranges from a few weeks to 2 years.
Beyond the 2-year point, active infection is rare. People developing active TB more than 2 years after exposure usually had a weaker immune system and coexisting medical condition.
This incubation period can be important globally. In areas with a high TB burden, the focus can be on treating latent TB. This would reduce the risk of a TB epidemic in high risk areas.
Because TB is a bacterial infection, healthcare professionals treat it with a combination of antibiotics. The course of antibiotics for active tuberculosis can last anywhere from 4 to 9 months.
Shorter regimens help you get through treatment faster, but a doctor will choose the regimen based on any existing medical conditions and potential for medication interactions.
The antibiotics usually used to treat tuberculosis include:
It's important to complete all the antibiotics in a treatment course in order to fully treat tuberculosis.
Cutting-edge DNA Sequencing To Speed Diagnostics
Next Generation Sequencing (NGS) technologies are allowing scientists to sequence DNA faster and expand knowledge of the genetic basis of disease. NGS is showing particular promise in areas where current diagnostic methods have shortcomings – such as HIV and TB – although there is some way to go before data can be interpreted meaningfully by doctors.
There is a lot of activity going on in the development of sequencing technologies. Over the past decade, suppliers have reduced equipment costs as they vie for a greater share of the market, to the extent that NGS platforms are nearing the $1,000-per-genome goal.
Illumina became the first company to receive US Food and Drug Administration (FDA) class II approval for a sequencing system for clinical diagnostics in November 2013 and also received clearance for its Cystic Fibrosis assay products based on this technology. Then, in September this year, Thermo Fisher Scientific listed its Next Generation Sequencing (NGS) system with the FDA for clinical use as a class II medical device.
So what benefits can NGS bring?
The NGS promise
When perfected, affordable NGS platforms with rapid turnaround times will offer significant advantages over quantitative polymerase chain reaction (qPCR) in genotyping. Unlike PCR methods, NGS has the potential to identify all the variants in a single experiment since it allows parallel sequencing and facilitates multiple gene analyses. Automation can make it less laborious and cheaper than Sanger sequencing, which is seen as the current gold standard. Labs can benefit from lower reagent costs, save instrument time and help physicians to make faster treatment decisions with affordable NGS tools.
NGS products will impact the genetic disorders and infectious diseases segments initially. Adoption of NGS assays in preference to qPCR could happen faster in clinical microbiology, where the pathogen sequencing platforms are almost comparable now in terms of speed and cost.
New NGS platforms are emerging, which are capable of completing typical bacterial genome sequencing quickly and cheaply. Automated platforms to interpret newly sequenced genomes are being introduced, which is crucial to make NGS viable, saving labour costs in data interpretation.
In terms of capital investments for instruments, competition among the big players is reducing costs significantly and various strategies are being adopted, with different systems available for different volume users.
Many small companies with single products are also active in the field, introducing innovative and affordable instruments. One example is a nanopore-based sequencing device of the size of a USB memory stick, with an average read length of 5,000 base pairs.
"Companies are also focusing on better accuracy through larger read lengths, which could be significant for over 10 per cent of the NGS market"
Companies are also focusing on better accuracy through larger read lengths, which could be significant for over 10 per cent of the NGS market. The short read length platforms employed for single-nucleotide polymorphism (SNP) detection would be useless for detecting gene variations that include large sequence deletions or insertions.
However, in spite of impressive advances, NGS is not expected to replace current genotypic and phenotypic methods, since most of them meet clinical lab requirements. Huge technical challenges exist but, as these are overcome, PCR assays could be overtaken in certain disease segments.
PCR dominance
The arrival of PCR in the 1980s revolutionised the clinical diagnostics field. The new capability to produce sufficient copies of target genes made laboratory tests faster and more accurate. During the restructuring period which followed, labs replaced genomic DNA with PCR-amplified DNA. The allele-specific detection assays soon evolved as high-throughput systems, enabling large-scale analysis of patient samples. Now PCR assays are some of the most common molecular diagnostic tools in these labs.
Our recent research has estimated that medical diagnostics accounts for about 43 per cent of the global demand for PCR technologies. Considering the market trends in clinical diagnostics and various alternative technology segments, we have forecast growth at 8 per cent CAGR between 2013 and 2018. However, advances in the NGS field in the past few months suggest that the impact of NGS on PCR demand may be felt sooner.
Shortcomings of PCR
The main issue with PCR assays is the need for additional confirmatory tests, which means treatment delays and added costs. For instance, PCR as a standalone tool is insufficient in genetic disorder diagnosis. Current practice is to follow up PCR tests with Sanger sequencing – particularly where rare genetic disorders are suspected.
Serious gaps exist in PCR-based infectious disease diagnosis as well. A typical example is the diagnosis of multidrug resistant TB (MDR-TB). Though antibiotic susceptibility detection through PCR is achievable theoretically, few PCR assays are available for routine clinical use.
"Having to run multiple tests to confirm susceptibility to each antibiotic can be costly, or even fatal"
Multiple strains with varying antibiotic susceptibility could be responsible for TB infection in a single patient. Hence, pinpointing resistance to all antibiotics at once is highly desirable. In a clinical lab, having to run multiple tests to confirm susceptibility to each antibiotic can be costly, or even fatal.
False positives can be a concern too.
Another drawback is the extensive time needed for designing and optimising PCR assays. Balancing PCR product size and efficiency is challenging as efficiency decreases with number of repeats. Identification and validation of critical biomarkers related to a particular disease or infection are complicated processes. Additionally, running so many PCR reactions to test each biomarker is not a viable option.
Possible applications for NGS
Disease areas where NGS will be adopted fast include HIV and TB diagnosis.
Conventional phenotypic TB tests delay effective treatments due to the slow growing nature of the mycobacterium tuberculosis complex (MTBC). PCR assays contributed significantly in TB diagnostics by speeding up the diagnosis time and enabling fast differentiation of MTB from non-tuberculosis mycobacteria.
Quick and accurate determination of antibiotic susceptibility of the MDR-TB strains, however, has not been achieved through PCR yet. Potentially, NGS assays enabling detection of resistance to all antibiotics at once can be more effective than PCR assays in this context. NGS-based whole genome sequencing of pathogens has evolved, making translation to clinical labs possible, and could make their entry into clinical labs soon.
HIV is another area where NGS assays can fill gaps. For example, viral tropism studies to determine the mechanism of the virus to enter host cells is crucial in determining the antiviral therapy suitable for an HIV patient. Frequent monitoring during the treatment period is necessary to diagnose resistance emergence. This can be achieved fast with NGS platforms.
Companies are racing against each other to tap the opportunities, particularly in the fields where qPCR has not been highly effective. At present a critical component missing in the conversion of sequencing data into clinically useful interpretations is the absence of fully automated systems with updated databases, which can assist doctors' treatment decisions. Hence, large scale switching to NGS is unlikely in the near term. Until then, PCR assays will continue their current dominance.
About the authors:
Quah Shun Ying is a research analyst at AcuBiz Consulting and Syamala Ariyanchira PhD is principal consultant at AcuBiz Consulting. They can be contacted by email: info@acubiz.Com.Co or phone: +6012 351 8258.
Have your say: To what extent will NGS technologies revolutionise clinical practice?
Honoring A Tuberculosis Trailblazer: Dr. Kathleen Jordan's Legacy In Focus At Granite Falls Exhibit
CATHY WURZER: I am glad you're listening to Minnesota Now here on MPR News. I'm Cathy Wurzer. So far this year, there have been 100 diagnosed cases of tuberculosis in Minnesota. TB is a highly contagious disease that was, at one time, the leading cause of death in Minnesota and across the country. In the late 20th century, schoolchildren were tested for TB as a way to detect the illness early before it became potentially deadly. Perhaps you had such a test when you were a kid.
There are still countless adults in the Granite Falls area who remember a doctor, Kathleen Jordan, who gave them TB tests in school. It's estimated Dr. Jordan performed more than 1.5 million TB tests on school kids throughout Minnesota in her career.
And to honor her work, there's an exhibit and a series of events happening in Granite Falls. Joining us right now with more on the doctor's story is Peggy Kvam of the Dr. Kathleen Jordan Project and Jill Heins, a national senior director with the American Lung Association in Minnesota. Such a pleasure. Jill, thanks for being in studio.
JILL HEINS: Thank you.
CATHY WURZER: And Peggy, thanks for being with us from Granite Falls.
PEGGY KVAM: Thank you.
CATHY WURZER: I want to set the scene for folks about Dr. Jordan. She really had an amazing background, for goodness' sakes. Peggy, can you kind of flesh her out for us a little bit? How did she get to Granite Falls?
PEGGY KVAM: Well, she was born in England. And her parents were Methodist missionaries down in Algeria. And that's where Kathleen was raised. Her parents ran an orphanage and a school down there. When it came time to go to college, she ended up going to a Methodist college in Ohio, near Cleveland.
And it was at that time that she decided that maybe medicine is her field of choice, and she enrolls in med school. But during I believe it was her junior and senior year in med school, she comes down with TB herself.
CATHY WURZER: Oh.
PEGGY KVAM: And she gets to go to a place in upstate new York in Saranac, the Trudeau Institute. And it was there that she met this good-looking young doctor, Dr. Lewis Jordan. And that's where they started their relationship.
Well, fast forward through med school, through her internship, she ends up engaged, and she comes to Granite Falls on a Sunday evening in August. By Monday, at 6:30, she was married in the house of a local doctor. And then she worked with the Riverside Sanatorium, which was one of 14 in Minnesota, and it covered a four-county area.
CATHY WURZER: Wow.
PEGGY KVAM: And so she started her medical career there.
CATHY WURZER: And we should say at the time, it was pretty unusual to have a female doctor.
PEGGY KVAM: There was only 4% of the doctors in the nation and in 1930 that were females. So, yeah, she was a rarity-- a pioneer, so to speak.
CATHY WURZER: Jill, and for folks not familiar with the sanatoriums that were all around the country-- Minnesota had several-- what were they used for?
JILL HEINS: They were specifically for individuals with active tuberculosis. And so tuberculosis, you can be infected with the bacteria, tuberculosis, and it can be latent in your body for weeks, months, or even years. And when your immune system is compromised, it becomes active. And so the sanatoriums were for individuals with active tuberculosis, so they didn't spread it to other people, as well as an opportunity for them to get at that time state of the art care and also recover.
CATHY WURZER: And TB, if my memory serves me correctly, just historically speaking, I mean, when there were outbreaks, it really scared people.
JILL HEINS: It did. At that time, in the 1920s, around one out of every 500 deaths in Minnesota was from tuberculosis. So, one out of 500. It was the number one cause of death at that time. Now, certainly, tuberculosis still remains worldwide and in Minnesota, but it's not the killer that it once was. We now have medicines to help treat that.
CATHY WURZER: So, Peggy, I mentioned in the introduction that a lot of school kids got the mantle tests. I'm trying to remember how they did it back in the day. But all of us had that, right? Did you get a test from Dr. Jordan as a kid?
PEGGY KVAM: Actually, I am one of Kathy's kids,
CATHY WURZER: Oh.
PEGGY KVAM: --as we refer to the group. You held out your left hand, your left wrist, and then she distracted you by suggesting that you're on a safari and you have a choice of-- and she gave you two different animals. And to be honest, I thought for sure there was a rhinoceros-- it's one of our school building because that's what I was concentrating so hard on seeing. She gives me this little shot. And if kids did react to it, she would kind of slap the wrist and say, oh, I got the mosquito.
She had a calming voice, strong French accent. But yes, she did travel to the four-county areas. And we actually have all of her records keeping, how many students in each grade level at each building, and how many were positive, and what the follow-up was. So it's really quite interesting.
CATHY WURZER: Jill, this is got to have been-- just given the amount of tests that she gave in her career, she must have been a pioneer in the public health field in Minnesota.
JILL HEINS: She was. One of the things that I found interesting looking through the American Lung Association's historical records-- was just amazing-- is how one day she would be in Little Falls, say, on a Tuesday, and the next day, she was in Waseca. So let's think about that. This is the 1930s.
Regardless of the weather and in the winter, cars don't go that fast. And she traveled from Little Falls, and then the evenings, she somehow got herself to Waseca for the next day, ready to work with school kids, test them, and provide education to the local health care professionals. She was a force of nature that we really need to recognize. One of the ways that Dr. Kathleen Jordan was able to do so much outreach and education across the state was her work was funded by Christmas seals.
CATHY WURZER: Oh, I remember those.
JILL HEINS: And Christmas seals exist today, but there are fewer and fewer people alive that have that memory and history. And so the Christmas seals are a funding stream and sold by the American Lung Association. In that time, it was all about education and prevention of tuberculosis, and now it's across all lung diseases and lung health.
CATHY WURZER: And of course, Christmas seals, for people who don't remember, I recall they were stamps with various designs on them. And you'd stick them on your Christmas cards.
JILL HEINS: You bet. That was really what funded all of her activities for additional testing and education in the community. So we're really thrilled to be able to have that connection with her. Interestingly, in the very beginning, Peggy was talking about how Dr. Kathleen Jordan, when she had TB, she went to a sanatorium in northern New York State to be treated and recover and was treated by a Dr. Trudeau. Dr. Trudeau was the founder of the American Lung Association.
CATHY WURZER: [GASPS] Interesting. I'm wondering, because of her efforts in education here, Jill-- and as we established, she traveled all around the state of Minnesota-- was there a lot of mis-- and disinformation about TB at the time?
JILL HEINS: I'm not completely sure. I think at that time, it wasn't called tuberculosis. It was called consumption. We didn't fully understand the disease at that time. And so a lot of the education was around make sure we have good nutrition, and make sure that you had plenty of fresh air.
There was an understanding that tuberculosis was spread through the air-- and that is correct-- from one person through the droplets, if they cough and sneeze and contracted by another one. But there was a thought that fresh air would really be the primary cure at that point.
CATHY WURZER: I'm wondering here, Peggy, when it comes to her stature in the Granite Falls community, I mean, she must have been revered.
PEGGY KVAM: Yes, she was. I think for the first 10 or so years, she was so busy traveling and giving her tests. And she not only educated the teachers, the schools, she also went around to any organization she could get her foothold in-- Kiwanis meetings, Jaycees, the Lutheran church people, or the Methodist. It didn't matter. She spoke everywhere.
She was a member of the Granite Falls UCC Church. She became active in teaching the Sunday school. She liked the older kids. That's when people really got to meet her. And then when she retired, she was the gentle little lady that walked around town, giving out her pink roses to her friends that might need a cheering up--
CATHY WURZER: Aw.
PEGGY KVAM: --a little bit. Yeah, she was loved.
CATHY WURZER: So, Peggy, why is it important to remember Dr. Kathleen Jordan? You've got events and an exhibit happening in Granite Falls. Why now?
PEGGY KVAM: We have people that still remember her. She lived such an extraordinary life. I think it's important that we honor that life of dedication. It was through her efforts locating and identifying and isolating and educating people that we were able to have a profound and lasting impact on the spread of tuberculosis, especially in the southwestern part of the state. And it helped to inform many public health discussions.
CATHY WURZER: And we should say, if my history is right, that Renville County, in your part of Renville County, had one of the highest rates of tuberculosis among school-aged children at one time. So--
PEGGY KVAM: Yes, it did.
CATHY WURZER: --she really did do amazing work. Really interesting conversation. Interesting effort in Granite Falls around this fascinating woman, and I'm glad that her history is not lost. Peggy Kvam, thank you. And Jill Heins, thanks for coming into studio.
JILL HEINS: Thank you for having us.
CATHY WURZER: Thank you. Jill Heins is the national senior director with the American Lung Association. She's based in the Twin Cities. Peggy Kvam is an organizer of the Dr. Kathleen Jordan Project, based in Granite Falls. Now, you can see the exhibit this coming Thursday through next Tuesday, the 16th, in Granite Falls. I'll have a link to more information on our web site, mprnews.Org.
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