Syphilis Is Evolving Like Never Before.. In Michigan

0:00 PC is a 43 year old woman,

0:03 presenting to the emergency room with headache, bilateral hearing loss.

0:07 Bi from Latin meaning 2 and lateral meaning sides.

0:10 And she had diplopia.

0:12 Diplo from Greek meaning double, and opia referring to a visual disorder.

0:16 She had double vision, in both eyes.

0:18 2 months ago, something was wrong.

0:20 She had a unilateral headache.

0:22 Uni meaning one.

0:23 It was just on her left side.

0:25 But, it was a pain that she had experienced before, she thought.

0:29 15 years earlier, when she was 28, she had an episode of shingles.

0:33 This is a time when chicken pox is reactivated.

0:35 PC is 43 right now.

0:37 This is happening in year 2022.

0:39 Meaning she was born in the late 1970s,

0:42 a time when 99% of children got chicken pox.

0:46 Varicella zoster virus causes chickenpox,

0:49 which later in life can reactivate to Shingles, also known as Herpes Zoster.

0:52 And it gets into the nerves causing very painful symptoms.

0:56 One of which is a particular feeling headache.

0:58 At the urgent care, given this history, and her symptoms at that time,

1:02 they gave her a 1 week course of antiviral medicine.

1:05 And the headache went away.

1:07 So they tried that medicine again

1:09 for this presumed SECOND shingles episode, 15 years later.

1:12 And it resolved the headache at the time.

1:15 But something else was wrong.

1:16 One month after the headache,

1:18 which is one month before she’s presenting to the emergency room now,

1:21 PC started having tinnitus, a ringing in her right ear.

1:25 She just woke up one morning with the horrible sound blasting on that one side.

1:30 But then her left ear started ringing too.

1:32 And both her eyes became bloodshot red.

1:35 At the Otolaryngology, Ears Nose Throat doctor’s office,

1:39 PC was found to have something going on, but nothing was conclusive.

1:42 Her auricles and her external auditory canals were normal.

1:46 Hearing tests confirmed she had hearing loss.

1:49 But reasons why were NOT found.

1:51 An MRI of her head showed nothing wrong.

1:54 PC was diagnosed with Sudden Idiopathic Hearing Loss.

1:57 Idiopathic meaning of an unknown cause.

1:59 She was given a 12 day course of steroids,

2:02 because many times, this could be inflammation related.

2:05 And things seemed to be fine at first.

2:08 But 4 weeks later, it was only getting worse.

2:11 The ears help maintain balance.

2:12 They do this through fluid-filled

2:14 semicircular canals that contain sensory cells.

2:16 This is called the vestibular system.

2:18 It relays signals to the brain.

2:20 One of the first things the doctor noticed,

2:22 was that PC’s balance was totally off.

2:25 And a repeat hearing test found that her hearing

2:28 got much worse over the last few weeks.

2:30 Given that balance is ear related, and that her hearing has gotten worse,

2:34 then it means something very terrible is happening.

2:36 It could be wrong with her nerves.

2:38 It could be something wrong with her brain.

2:40 She was given an urgent referral to a rheumatology clinic,

2:43 one who specializes in autoimmune diseases.

2:45 And they set the schedule to see her in just 3 days.

2:49 But she wasn’t going to make it to 3 days.

2:52 Hey, have you learned something from this video so far?

2:55 If you have, and you aren’t subscribed yet,

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3:05 I do these videos for fun,

3:06 and they are to teach medicine by showing cases, and their associated stories.

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3:19 Appreciate you.

3:20 PC had polyarthalgia.

3:21 Poly meaning many, and arthr referring to joint.

3:25 -algia meaning pain.

3:26 Her entire body hurt.

3:27 She started seeing spots in her field of view.

3:30 Her head was pounding so hard,

3:31 she wasn’t going to make it to the rheumatology visit.

3:34 She drives herself to the emergency room where we are now.

3:38 At examination, PC physically looked fine.

3:40 A blood test finds she has some kind of inflammation happening.

3:44 Every other everyday vital sign was fine.

3:46 Her blood pressure, heart rate, breathing, all normal.

3:49 No fever.

3:50 Looking at her eyes, doctors found inflammation there.

3:52 At this hospital, they did the tests again and confirmed:

3:56 PC did have hearing loss.

3:57 One ear was worse than the other.

3:59 And she couldn’t balance herself.

4:01 But it was just these four problems.

4:04 Given her headache, polyarthralgia,

4:06 asymmetric sensorineural hearing loss with vestibular hypofunction,

4:10 and ocular inflammation, doctors have some clues as to what’s happening.

4:14 They write a list of problems that can cause all of these together,

4:18 and they need to rule out each one to figure out exactly what’s happening.

4:22 PC’s problem started 8 weeks ago with a headache that may have been shingles.

4:26 4 weeks if you only count the hearing loss.

4:28 This pace is important.

4:29 If these problems came up in 8 seconds instead of 8 weeks,

4:33 then you would think that the problem is vascular.

4:35 Blood vessel.

4:36 So, with a headache, you’d think stroke.

4:38 If it was 8 years, you would think of cancer.

4:40 That a tumor has grown somewhere in her body

4:43 and has finally manifested its symptoms in a way perceivable,

4:46 obvious and rapidly degrading her quality of life.

4:49 But despite her current problems coming up in just weeks,

4:52 she did have a SUSPECTED shingles reactivation 15 years ago.

4:56 What if that wasn’t Shingles?

4:59 Leukemia can create blood cells that infiltrate

5:02 nerve tissue causing sudden hearing loss.

5:04 Tiny little tumors that have spread throughout the body

5:07 can also get in and do the same thing.

5:09 But there’s a very easy way to find out if this is happening.

5:13 Tumors would be in the brain.

5:14 That means we can see that on the MRI.

5:16 And when doctors did a brain MRI, it looked normal, so she doesn’t have cancer.

5:21 But if we know her problem is inflammation, what else could this be?

5:26 It could be autoimmune.

5:28 Auto meaning self.

5:29 But which disease affects the eyes and the ears simultaneously, like this?

5:34 Lupus actually can do this.

5:36 But it typically affects eye blood vessels, when it does.

5:40 And she doesn’t have that.

5:42 She also doesn’t have other symptoms of Lupus.

5:44 There’s a disease where the immune system inflames

5:47 the spine completely disabling a person known as ankylosing spondylitis.

5:51 In the immune overreaction, this can cause permanent hearing loss,

5:55 but when it affects the eye, it typically only affects one at a time.

5:59 And she doesn’t have anything wrong with her spine.

6:02 Every single autoimmune problem that PC could have,

6:05 would exhibit hearing and vision loss in ways different than what she has.

6:09 And she also doesn’t have any of the disease

6:11 defining problems of any of these, except for one, so this is marked as a maybe.

6:16 The only way it could be this is if it isn’t anything else.

6:20 Which brings doctors to the final inflammation category.

6:23 Infection.

6:23 Lyme disease.

6:24 It’s caused by a bacteria named Borrelia

6:28 burgdorferi that comes from a tick bite.

6:30 PC is in Michigan.

6:32 Michigan has ticks.

6:33 Lyme Disease causes polyarthralgia, vision loss, hearing loss and vertigo.

6:37 Borrelia is spiral shaped bacteria called a spirochete.

6:41 Doctors sent PC’s blood samples to test for this.

6:44 But a different spirochete, that also causes all her symptoms but forms

6:49 an entirely different disease is Treponema pallidum,

6:52 the bacteria that causes syphilis.

6:54 Because PC is having neurological signs and symptoms,

6:58 doctors stick a needle into her back to draw some of the fluid

7:01 that cushions the spine and the brain called cerebrospinal fluid CSF.

7:04 If her problem is syphilis,

7:06 then it means that the bacteria has gotten in to her brain.

7:11 And when the tests returned, they found out, PC has syphilis.

7:15 But, something was wrong.

7:16 When doctors found syphilis,

7:17 they reported it to the Michigan Disease Surveillance System.

7:20 And when the Michigan Department of Health and Human Services got the report,

7:24 they immediately opened an investigation,

7:26 because there was much more to this case.

7:30 5 weeks earlier, a 50-year-old woman presented

7:32 to the emergency room with blurred vision.

7:34 She was in a panic because she was scared that she was going blind.

7:39 There were multiple sores between her legs.

7:41 Her primary care doctor believed this to be a herpes simplex virus reactivation.

7:45 But in the hospital, they found out.

7:47 That wasn’t herpes, she had syphilis.

7:49 When they asked her about intimate partners,

7:52 she gave the name of a man that she had met on the internet 2 months earlier.

7:56 And she didn’t have any close contact

7:58 with anyone else for more than 12 months prior.

8:01 2 weeks later, in the same emergency room.

8:03 A third person, a 60-year-old woman,

8:05 presented to the emergency room with hearing loss,

8:08 blurry vision and double vision.

8:10 But she had trouble moving her eyes.

8:12 Her face was drooping.

8:13 They thought she was having a stroke,

8:15 but physical exam found… lesions between her legs.

8:18 And when they tested further, they found out this woman also had syphilis.

8:22 When they asked her about intimate partners,

8:24 she gave the name of a man she met on the internet 2 months earlier.

8:28 And she also didn’t have any close contact with anyone else for years prior.

8:33 The reason why Michigan Department of Health

8:35 and Human Services opened an investigation,

8:37 is because the name of the man given by these 3 women, was the same.

8:41 All 3 women had met him with close contact,

8:44 in just the timespan of a couple of weeks.

8:47 Public health officials called this man.

8:49 He picked up.

8:50 But he didn’t have much to say.

8:51 They scheduled a visit for him to come

8:53 in and see one of their public health doctors.

8:55 And he agreed to a set time and day.

8:58 But he didn’t show up.

8:59 A couple weeks pass.

9:01 At an emergency room, in another southwest Michigan county,

9:04 a 45 year old woman presents to the emergency

9:07 room with blurred vision and a rash on her hands.

9:10 The inflammation in her eye looked very particular.

9:12 When they tested her, they found syphilis.

9:14 She had had close contact with 3 people in the last 6 months.

9:18 2 of the men tested negative for syphilis.

9:20 And when she gave the name of the most recent person,

9:23 it was the same name as given by PC and the 2 other women.

9:28 And it still wasn’t finished.

9:29 At yet another emergency room in a neighboring county, still in Michigan.

9:33 A 51 year old woman presented with visual floaters,

9:37 seeing flashing lights, and worsening vision.

9:39 These came 3 months earlier when she had cataract surgery.

9:42 So they thought that that was responsible.

9:44 But not even a few weeks later, when this woman came in with headache,

9:48 confusion, and stiff neck, they found out that she had syphilis.

9:52 And when they asked her about recent intimate contact, she listed a few names,

9:57 one of which, was the same name given by PC, and the 3 other women.

10:01 All of these cases tracing back to the same person.

10:04 Syphilis, as we know it today,

10:07 was first documented clinically in the late 1400s.

10:09 But, humans didn’t know that bacteria caused it until 1905.

10:13 And 92 years after that, Treponema pallidum’s entire genome was sequenced.

10:17 So we happen to know a lot about this particular bacteria.

10:21 Which means when health officials finally got to meet

10:24 the common intimate partner of these 5 women, they noticed something weird.

10:28 A local public health physician reviewed this man’s medical records

10:31 around the time PC’s case was reported to the state.

10:34 They found out, he had gone to the same

10:37 emergency room as one of the other women, 2 months before he met PC.

10:41 The medical record logged that he had ulcerative

10:43 lesions on not only the part between his legs,

10:45 but he also had a rectal lesion too.

10:48 He had told doctors here,

10:49 that he had had intimate contact with a 60 year old woman just a day earlier.

10:54 This would turn out to be the same 60 year old

10:56 woman who presented to the emergency room 3 weeks before PC.

11:00 When doctors asked further,

11:01 he stated that he had multiple female partners in the last 12 months.

11:06 And all of them were women.

11:08 Typically, early syphilis for men presents as 1 lesion.

11:11 It’s called a chancre.

11:12 And that chancre doesn’t usually show up the immediately the day after.

11:16 What can show up as multiple lesions, much quicker, is herpes.

11:20 And so this man was tested for herpes.

11:22 But it was negative.

11:23 Sometimes the test isn’t right.

11:24 And he was discharged with medicines for herpes.

11:27 No syphilis was testing done,

11:29 therefore the Michigan Disease Surveillance System didn’t get the report.

11:32 And it was from here, where he continued to have intimate

11:35 contact with local women in neighboring counties,

11:38 all along the southwest Michigan region.

11:40 But this wasn’t the weird thing that public health officials noticed.

11:44 All 5 women had blurred vision, and thus, ocular syphilis.

11:47 And this happened just weeks after their initial infection.

11:51 Syphilis that has systemic symptoms like this, this quickly, should be rare.

11:55 If it does happen, it’s most recorded with HIV co-infection,

11:59 and with male to male contact.

12:01 People who misuse substances by injection are also

12:04 at risk of getting more severe syphilitic disease.

12:07 But none of these 5 women fit any of this criteria.

12:11 All of this, stemming from a single common intimate partner,

12:15 suggests that an unidentified strain of Treponema pallidum was transmitted here.

12:20 Data typically hasn’t logged majority women to experience this kind of disease.

12:24 And this is where some connections need to be made.

12:27 In 2015, Seattle.

12:28 4 men were reported by local hospitals to have come in with vision loss.

12:33 They were diagnosed with uveitis.

12:35 Itis meaning inflammation of the uvea, the middle layer of the eye’s outer wall.

12:40 Further testing found all 4 had syphilis.

12:42 They were men who had intimate contact with men,

12:45 and 2 of them, knew each other, they were partners.

12:48 3 of these patients recovered some eyesight after syphilis treatment,

12:51 but one was permanently blind.

12:53 2 months later, in San Francisco,

12:55 8 patients with ocular syphilis were reported to the CDC.

12:58 1 was a woman, 7 were men of which 6 had intimate contact with other men,

13:03 and only the straight man did not have HIV.

13:05 7 patients recovered some vision after syphilis treatment

13:09 and one was permanently blind in one eye.

13:12 In 2015, syphilis cases in the United States had been rising for 15 years.

13:17 It would go higher, too.

13:19 Before 2015, CDC didn’t have a good way to record ocular syphilis.

13:23 In fact, PC’s situation where her hearing loss was diagnosed as Idiopathic.

13:28 That there was no known reason for the hearing loss.

13:31 Well, there was an ocular version of that that was

13:33 happening to syphilis patients at the time.

13:35 An eye doctor would just treat the uveitis

13:37 without finding the patient’s underlying syphilis, or, the patient,

13:40 just under the notion that they might have an eye infection,

13:43 could have just taken treatment that did nothing for the syphilis.

13:46 And then gone on to have intimate contact with more people,

13:50 passing on the Treponema before becoming permanently blind.

13:53 So in 2016 following these reports,

13:56 CDC issued a clinical advisory and an easier way to report ocular syphilis.

14:01 And this is where we will start hypothesizing.

14:04 Do you remember that we sequenced Treponema pallidum’s genome in 1998?

14:08 Well, since then, we have a decent idea of what

14:11 strains are around in different regions in the United States.

14:15 In 2016, 63 patients with syphilis in Seattle gave samples,

14:19 where Treponema genome was sequenced.

14:21 They wanted to see if ocular symptoms were being caused by a specific strain.

14:26 18 of them had ocular syphilis.

14:28 And from them, at least 5 distinct strains of Treponema were identified,

14:32 of which, one unusual strain was detected.

14:35 Different from the other ones with and without ocular syphilis.

14:39 On its own, this study didn’t find clear evidence

14:42 that this increased incidence of ocular syphilis was absolutely,

14:46 100% because of an unknown strain.

14:48 But newer evidence since then,

14:50 suggests that the bacteria is changing in a way that we’ve never seen before.

14:55 In 2023, a 32 year old man in Seattle came

14:58 into the emergency room with fever and purulent urethral discharge.

15:01 Purulent meaning that there was pus.

15:03 He told the admitting nurse that he had an intense pain between his legs.

15:07 And all of this came a few days after intimately interacting with a woman,

15:11 different from the woman who he lived with and normally interacted with.

15:14 And he said that that woman he lived

15:17 with was newly diagnosed with HIV 4 weeks earlier.

15:20 This particular man was newly diagnosed,

15:22 at this emergency room visit, with acute HIV.

15:25 They found a single chancre between his legs,

15:28 and unlike the 5 women from Michigan,

15:30 he was tested for syphilis right then and there.

15:32 And it came out positive.

15:34 He was given antibiotics in the emergency room,

15:36 and given additional antibiotics to take at home.

15:38 These would clear out the Treponema

15:40 and prevent syphilis from progressing further.

15:42 And he was scheduled for an appointment to start HIV treatment.

15:45 But he never showed up for that appointment.

15:48 Over the next 15 months,

15:49 this man would be in and out of urgent care and the emergency room.

15:53 He’d have severe abdominal pain, blurred vision, and a shooting pain up his leg.

15:56 But every time, just before they’d treat him, he would leave.

16:00 18 months after his initial diagnosis,

16:02 the symptoms were so severe that this man presented to the emergency room.

16:06 By this point, he had lost 40 pounds, lost most of his hair,

16:09 and he had become blind in his left eye.

16:12 When doctors sent a camera down his throat to look in his stomach,

16:15 they found multiple ulcers.

16:16 They took samples from these to test, and they found Treponema pallidum.

16:20 Doctors sent another camera through his other end and found inflammation.

16:25 And they took even more samples.

16:27 And this is where further evidence that Treponema is changing, appears.

16:30 When the Treponema genome from this man’s ulcers were sequenced,

16:34 doctors found there were 2 distinct strains present.

16:37 This man had told doctors that he only ever had intimate contact with women.

16:41 But he hadn’t for several months at this point because he had become so sick.

16:46 Meaning, at the time of infection,

16:47 he may have been infected more than once, simultaneously.

16:50 But also found, was that both strains’ DNA featured mutations not yet observed,

16:56 meaning that the bacteria may have undergone intrahost evolution.

16:59 This might have been from the fact that he discontinued treatment shortly

17:04 after his initial diagnosis 18 months

17:06 earlier and possibly with his HIV coinfection.

17:08 But all of this led to the most unique finding.

17:12 Some specific genes were discovered that were

17:15 a combination of both strains together.

17:17 You can’t get these specific genes without putting these two strains together.

17:21 Meaning that both bacterial strains had gathered together,

17:25 and were creating a brand new strain of syphilis through genetic recombination.

17:30 Given that this man had extreme ocular symptoms

17:32 to the point of becoming blind in one eye,

17:35 and that this is happening about 8 years after

17:38 the CDC issued the clinical advisory on ocular syphilis,

17:41 this is another signal for us to consider,

17:43 that syphilis is changing in a way that we’ve never seen before.

17:47 And this brings us back to PC’s case.

17:49 When she was found to have ocular and neurosyphilis,

17:52 she was given intravenous penicillin.

17:54 When syphilis is found early,

17:57 and there aren’t that many Treponema bacteria floating around,

18:00 it’s usually one dose, intramuscularly.

18:01 When syphilis is in the brain, and the nerves,

18:04 like in PC’s case, the intramuscular dose can’t get into the brain.

18:08 Cant get into the nerves.

18:10 But Intravenous Penicillin can get in, so it

18:12 was given every 4 hours for 2 weeks.

18:14 There’s several things that are true, that may or may not be connected here.

18:18 First, syphilis cases in the US have been going up since year 2000.

18:23 Second, HIV co-infection makes syphilis

18:26 disease worse because of immune deficiency.

18:29 Third, the prevalence of ocular syphilis cases appears to be increasing.

18:33 This may have been happening before the CDC advisory in 2016, however,

18:37 the increase could also be attributed to the fact

18:39 that we are paying more attention to ocular syphilis.

18:43 Fourth, Treponema pallidum is changing through genetic recombination.

18:47 We have documentation going back decades

18:49 that this particular bacteria changes slowly.

18:52 But we’ve now been able to directly observe that different

18:55 strains can and will recombine genetically to create new strains.

18:58 It’s not to say that this has never happened before,

19:02 it’s just that we now have evidence of seeing it first-hand.

19:06 These 4 things are not an exhaustive list, there’s probably a lot more.

19:10 But if we just look at these 4, a few questions come up.

19:14 If the cases have been increasing, and there’s a situation whereby the bacteria

19:18 can cause a different-looking illness in humans,

19:21 and given that the bacteria can and has changed in ways we haven’t seen before,

19:26 is it possible that certain new strains are

19:29 causing more cases of, and more severe, ocular syphilis?

19:32 Will these changes in the bacteria create

19:35 a different syphilis with different signs and symptoms?

19:37 And maybe the worst question that we could think of right now:

19:41 from these changes, can an antibiotic-resistant strain of Treponema emerge?

19:45 We saw it happen in the early 2000s.

19:49 Another antibiotic called azithromycin was able to treat syphilis.

19:52 This was for the patients who were allergic to penicillin.

19:55 But since around 2002, we can’t use it anymore,

19:58 because the bacteria is completely resistant to it now.

20:02 But that recombination paper from Seattle says

20:04 that that particular recombined strain didnt feature penicillin resistance.

20:08 And the question that we might not ever know,

20:11 because doctors weren’t able to take samples from PC or the 4 other women,

20:15 or from the 1 common partner they interacted with, is did they have an unusual,

20:21 undocumented bacterial strain passed among them?

20:23 One that caused their ocular syphilis of this severity,

20:27 in such a short amount of time?

20:29 No matter what, we have this case now to refer to going forward.

20:32 Syphilis isn’t going anywhere anytime soon.

20:34 Public health campaigns have been raising awareness about it.

20:37 Which by the way, please see a medical

20:39 professional if you believe you may have been infected.

20:42 And don’t wait.

20:42 And don’t pass it on to others.

20:45 And with research and application of past experience,

20:47 we should be able to soon answer some

20:50 of the questions about Treponema pallidum, and the disease.

20:53 With the right treatment finally, after the right diagnosis,

20:57 PC was able to make A recovery.

20:59 The other women and the common partner did receive some treatment.

21:03 And presumably they did recover some.

21:05 Thanks so much for watching.

21:07 Take care of yourself.

21:08 And be well.