How long should a diagnosis for typhoid fever take?

Factual Questions
1

In this thread I bemoaned the fact that I had very likely been exposed to typhoid fever. I also had some symptoms that could have been of a mild case of this disease, but might not have been. I promptly visited my doctor and got a blood sample taken that was to be sent out to see if I was by any chance a (currently) symptom-free carrier, or what. That was a week ago. Every day I call the doctor’s office and every day they say nothing has come back. Today the nurse/receptionist/whatever told me that since this was a highly unusual test to be requesting, maybe it was just not being given a high priority.

This seems kinda bogus to me. I mean, sure, it’s important to have the results of a cholesterol test come back promptly, but it’s not like your high cholesterol is going to endanger anybody else. OTOH, maybe this is a test where you have to let a culture run for a week, or something. To make me even more paranoid, my daughter, who lives with me, is now starting to run a bit of a fever and is having some digestive difficulties.

Which leads to my question, in hopes that someone out there knows the answer:

How long should it take for whatever tests might be involved to produce results?

2

Typhidot looks like a pretty simple double antibody test (see procedure link) to me; maybe half a day when you include incubation and washing steps.

3

In Canada, I’d have to send the test to a provincial lab. It would take me 1-2 weeks to get the result. If there was a crucial need to get the test result as quickly as possible – there was a genuine public health risk, for example – I’d get an infectious disease specialist involved and would get the results in a day or two – but this level of urgency would not be justified in most cases.

4

(Before you answer, yes, I am aware typhoid is a public health risk. I cannot control the speed which the provincial lab does this sort of test. In the Canadian health system, you generally can get things done quickly with a compelling reason – and the patient, myself, and an infectious disease specialist would probably define this differently.)

5

Thanks for the quick replies. I don’t know where my doctor had to send the specimen for testing, but I do know she consulted with a local infectious disease specialty group that is not that far away. At least now I know what question to ask next. I suppose if there were others in the area with confirmed cases, or if I were a restaurant cook, there would be some need for a hurry-up.

6

Check on or about page 62 of this cheerful thing.

The CDC on Typhoid Fever

The ball-park figure for incubation period is something like two- to three-weeks after exposure (here, and here

7

If you had read her previous thread, you would have seen that she is well aware of those facts, and that the CDC page was also linked there.

8

Remember that public health labs test a lot of reportable diseases, and your specimen would join the line. Many of these diseases present with vague symptoms. And in the absence of an epidemic, or more severe symptoms, or public health crisis… this test should be done as soon as they can, but not emergently.

9

Generally, unless there is a pressing need, these are sent away to labs and pooled until most of a 96-well ELISA plate can be filled. This can take weeks. Even in a best case scenario, any send-away labs generally take at least a week.

For culture, if it is done in a hospital lab, I’d imagine it could be cultured in a four or five days maximum. It is generally difficult to culture Salmonella, though, because the infection is transient. Typhoid, as I’m sure you’re aware, can be carried in the gallbladder and the gastrointestinal tract. Stool and blood cultures are not great for the diagnosis, and maybe a more sensitive assay like PCR may be required. This is not a slow test, but specialized tests are always slower because they are rarely done.

10

Thanks again for the info and the links. What a great place this is!

So I guess I can forget about complaining to anyone, be grateful that if I did have the thing I didn’t get as horribly sick as I might have, and continue my now compusive excessive hand-washing.

By the way, what’s a PCR?

11

PCR stands for Polymerase Chain Reaction, which is basically a method to amplify a little snippet of DNA so that you can look for it in a sample.

To ID your illness as typhoid, for example, we could be looking for a specific gene that’s characteristic of the typhoid bacterium. Except, in the blood sample you’re giving, there may not be enough bugs, and enough copies of the gene, to detect. So first, we’d have to use the PCR technique to multiply the copies of that gene (and the beauty of it is that it’ll only copy a teeny bit that you’re looking for, and not ALL the DNA), so that we can run the tests looking for it.

12

Fascinating. So some procedure will multiply a specific bit of DNA if there’s any of it in any part of a sample? They don’t have to actually find a bacterium (if that’s what you call one of those) first?

Please excuse my ignorance here, but I’m imagining somebody looking through a microscope for something that looks like bacteria. I always thought that the bacteria were identified visually. Apparently not.

My only previous experience with something like this is when my kids got throat swabs to look for strep. In the “long” version, I was told that they simply wipe the swap on a culture medium, put it in the appropriate environment, and then look to see what grows overnight. Or when they took a blood sample for mono and the results also came back overnight. But then both of these examples are things for which hundreds, if not thousands, of samples must come in every day.

13

The answer to your question is “no.”

Sure, the standard infectious disease way to go about things is to begin with culture and stain. Stain, meaning to take the clinical specimen, add dyes, and look under a microscope. Culture meaning that we can take the clinical specimen and using fancy algorithms and culture media, determine what grows and how it looks to decide what bacteria and in there. Nowadays, of course, you just draw blood into a few liquid culture bottles containing who knows what reagents and a few days later you stick it into a fancy computer which identifies which bugs are in there.

Culture and stain is good for diagnosis of a lot of the big illnesses – namely urinary tract infections, strep throat, pneumonia, tuberculosis (no culture, just stain), and others. There are many reasons why we can’t use it – the causative agent is too small for staining or is invisible to stain (like viruses, rickettsial diseases, and Chlamidya for example). Or it doesn’t easily culture (like viruses, Treponema pallidum, TB). In theory, culture can detect if only one bacterium is present. In practice, since everything is covered with bacteria, it doesn’t work like that even for hardy bacteria. This is particularly true of a disease like typhoid which may wax and wane and have lots of variability in the clinical samples. Certain clinical samples are more difficult to deal with than others (for instance stool). And while staining is fast, culture takes at least 3 days. So other strategies (immunoassays and PCR specifically) have been designed. Immunoassays are routinely used for rapid diagnosis – you mentioned two (the monospot test for mono and the strep throat swab). In-office rapid strep tests take 15 minutes. PCR is the most sensitive assay out there, it can be quite fast, but it is usually something processed by bigger diagnostic labs. So this slows things down.

If you properly design a PCR strategy, you can detect one piece of DNA in your input sample. The key, obviously, is the “proper design” part – obviously even if you have a little wiggle in your design, if you have a few billion bacteria to begin with, a 10,000 fold weed out is still incredibly noisy. Luckily, good PCR strategies aren’t particularly difficult to construct, especially with the large-scale sequencing of many bacterial genomes. PCR works by amplifying DNA between two designed short pieces of DNA called primers. If the primer sequence exactly matches your bacteria of interest and nowhere else in nature (which is not uncommon given evolutionary divergence), then your PCR will amplify only your region and nowhere else in nature. Naturally, if you don’t have your bacteria in your input, you won’t get PCR product. If you do, then you will. Voila, diagnostic test. Add in FDA approval, lots of science about sensitivities, specificities, failure rates, etc, and you are ready to take it to market.

14

Rather, the first answer is “yes”, the second answer “no.”

15

The molecular infectious disease lab at my company is right next door to ours. I don’t think they offer a typhoid PCR test, but I could be wrong about that. But at least in our MID lab, every test is run twice a day on weekdays and once on the weekends. The only delay would be in getting the sample to us and, rarely, if they needed to repeat the test for some reason.

Incidentally, we’ve proved that for one of our genetic assays currently being run clinically, we can get detectable amplification with less that one whole genome present in the reaction. That is, even if we have a grand total of one chromosome there, we can pick it up. Of course, it wouldn’t give you an accurate genotype, since you need both the maternal and paternal chromosome for that, but that gives you an idea of the sensitivity we’re looking at.

16

This is all wonderfully interesting. It’s amazing what can be done. Thank you.

Oh, and BTW, I got a call from my doctor this morning. Test negative. sigh of relief

17

That is good news. :slight_smile: