Markers of exposure to spotted fever rickettsiae in patients with chronic illness, including fatigue..., 2008, Unsworth et al

[Hutan]

Abstract
Background: Some investigators believe that a proportion of chronically unwell patients, many with fatigue, have an underlying rickettsial disease.

Aim: To investigate the prevalence of markers of rickettsial infection in patients with chronic illnesses.

Design: Observational study.

Methods: A 526 patient cohort with chronic illnesses from Melbourne, Australia and 400 control patients from Newcastle, Australia were assessed using serology, culture and PCR for the detection of rickettsiae. Rickettsial serology was performed on another cohort of 581 chronically unwell patients (and 34 non-fatigued patients from the same practice) from Adelaide, Australia.

Results: Of the Melbourne patient cohort, 14/526 (3%) were real-time PCR positive for rickettsial DNA compared to none of the 400 control patients (P < 0.001). Of these 14 patients, Rickettsia honei strain ‘marmionii’ was detected in 5 and isolated from 2. Rickettsaemia was seasonal, with more in winter (8/145; P < 0.03) and less in spring (0/143; P < 0.03). Positive rickettsial serology titres of ⩾1:256 were seen in 206 (39%) patients. Of the Adelaide patient cohort, 238/581 (41%) had positive rickettsial antibodies titres. Of the 34 control sera, 5 (15%) were serologically positive (P < 0.002). Both Melbourne and Adelaide patient cohorts had significantly higher seropositivity than the Newcastle control cohort (3/399; P < 0.0001).

Conclusions: In patients with chronic illness, rickettsial DNA in peripheral blood and/or rickettsial seropositivity may represent exposure to rickettsiae or underlying rickettsial diseases. It is not known whether the presence of rickettsiae is causally related to the patients’ chronic illnesses, or reactivation of a latent rickettsial infection.

https://academic.oup.com/qjmed/article/101/4/269/1545064
N. Unsworth, S. Graves, C. Nguyen, G. Kemp, J. Graham, J. Stenos

 

[Hutan]

I've posted about this old paper before, but I think the detail must have been on Phoenix Rising.

I wasn't in this study, but I have tested positive to rickettsias.

Rickettsiae are small obligate intracellular bacteria usually transmitted to a human via the bite of an arthropod, often a tick. Rickettsial disease usually has an acute onset and has major symptoms of headache, rash, fever, myalgia, arthralgia and fatigue.25

Most cases of acute rickettsial disease resolve without complication after antibiotic therapy, however, cases of Brill–Zinsser disease, a recurrent form of epidemic typhus (Rickettsia prowazekii), are well documented decades after the initial infection.26 Cases of persistent scrub typhus (Orientia tsutsugamushi) infections in humans27 and rickettsial spotted fever infections in dogs28 have also been documented. Thus it is reasonable to speculate that spotted fever group (SFG) rickettsia may also be able to cause a chronic infection or be associated with a chronic illness.

 

[Hutan]

It's a not a perfect study. The chronically unwell cohorts were not well characterised, and neither were the controls.

The pattern of rickettsial serology in the 14 patients who were rickettsial DNA positive (only 5/14 seropositive) was not dissimilar to the seven acute rickettsial patients with FISF.33 In the current 14 cases the failure of some patients to seroconvert is not understood and may have been due to the extremely low quantity of rickettsial DNA/organisms circulating in the patient's blood. The Melbourne and Adelaide cohorts’ serology findings were not dissimilar, with 39 and 41%, respectively having positive rickettsial serology.

It is unclear if the underlying rickettsaemia is (partially) responsible for the patients’ chronic ailments or simply a reactivation of a latent infection caused by immunosuppression generated from the chronic condition itself or the treatment thereof.

There was thinking about t-cell activation from latent infections back then:

Gene expression studies in patients with chronic fatigue syndrome revealed an increase in T-cell activation.39 Although a cytotoxic T-cell response is an important factor for eradicating a rickettsial infections,40 chronic antigenic stimulation of T-cells may be responsible for fatigue induced as a result of an aberration in the patient's immune response. It has been postulated that post Q-fever fatigue syndrome, along with its cytokine dysregulation, may be caused by a similar chronic antigenic stimulation.20,22–24

So, only 5 of the 14 people who had rickettsia DNA in their blood were recorded as positive to rickettsia antigens using the standard test.

The number of rickettsia found in the patients’ blood was very low, being detectable in most cases only by a highly sensitive and specific rickettsial real-time PCR.31 The amplicons of the citrate synthase real-time PCR assay are very small (74 base pairs) and cannot be sequenced. The low sensitivity of the traditional gel-based 17 kDa PCR may explain why only 5/14 real-time PCR positive patients were positive with the traditional assay. Hence it was not possible to determine the rickettsial species present in the other nine patients.

 

[duncan]

Supposedly Willy Burgdorfer was convinced that what was making all those people get and stay sick back in the late 70's was Rickettsial. No one is really clear on why he changed his mind suddenly to a Borrelia spirochete since he found both in virtually all the same samples from sick individuals.

Of course, testing eventually demonstrated Lyme was due to a spirochete.

I still wonder why they aren't testing for Rickettsia to see if a pathogen tandem is involved in generating severity and chronicity, but oh well.

 

[Hutan]

I find the lack of followup on this result odd.

One of the authors is Professor Stephen Graves who runs the Australian Rickettsial Reference Laboratory which I think is a mainstream legit lab, mostly focussed on Q fever. Professor Graves was kind when I contacted him after getting the positive rickettsia result early in my illness, although was not able to help further.

 

[Sly Saint]

COMMENTARY: IS THERE A SCIENTIFIC BASIS FOR TREATING PATIENTS WITH CHRONIC FATIGUE SYNDROME WITH PROLONGED COURSES OF DOXYCYCLINE?
CommDisBull 10(2)-May final2012.pdf (nicd.ac.za)

might contain info of interest.

(another 'treatment' I tried early on (although it involved two types of anti-biotics), due to articles about rickettsia and also chlamydia pneumoniae being implicated in ME.)

*****
This can be discussed more on the Antibiotics thread

 

[duncan]

They should be able to tell us. They should have all rickettsial diseases well-characterized by now. They should have unquestionable yes-or-no diagnostics available anywhere any time Rickettsia falls into a differential diagnosis.

You can replace "Rickettsia" with any number of infections: Herpes, Borrelia, Bartonella, Babesia, just off the top of my head.

The state of Medical acumen is blunted, maybe beyond repair in my lifetime. It's a bleak joke.

 

[Art Vandelay]

I find the lack of followup on this result odd.

One of the authors is Professor Stephen Graves who runs the Australian Rickettsial Reference Laboratory which I think is a mainstream legit lab, mostly focussed on Q fever. Professor Graves was kind when I contacted him after getting the positive rickettsia result early in my illness, although was not able to help further.

One of the authors, John Graham, was a specialist physician who continued to help people with ME/CFS after he retired. I never saw him but exchanged emails with him on occasion. He unfortunately suffered from significant health issues that stopped him seeing patients quite some time ago.

On the basis of this hypothesis, I was tested for rickettsia at Graves' lab. My test was negative but a later test for Borrelia at the same lab was positive (IgM). I believe Graves has earned the ire of many whose illness began after a tick bite by marking all positive tests for Borrelia as "false positive" as he claims that Borrelia doesn't exist in Australia.

 

[Joan Crawford]

They should be able to tell us. They should have all rickettsial diseases well-characterized by now. They should have unquestionable yes-or-no diagnostics available anywhere any time Rickettsia falls into a differential diagnosis.

You can replace "Rickettsia" with any number of infections: Herpes, Borrelia, Bartonella, Babesia, just off the top of my head.

The state of Medical acumen is blunted, maybe beyond repair in my lifetime. It's a bleak joke.

Totally agree @duncan

It is shocking that patients and their doctors fly blind about these infections still. And likely will do for the foreseeable. A few brave doctors have stuck with clinical diagnoses, variable quality of tests and my reaction to various medications with success, but it should not be this lottery, nor should so many patients remain so ill with few, if any, treatment options. Profoundly sad place to find ourselves in 2023