Borrelia miyamotoi

Topics with information and discussion about published studies related to Lyme disease and other tick-borne diseases.
dorothy de kok
Posts: 64
Joined: Fri 2 Nov 2012 15:03

Re: Borrelia miyamotoi

Post by dorothy de kok » Fri 14 Dec 2012 5:48

Thanks CO.
Exactly the stuff I was looking for.
Dorothy

Lorima
Posts: 914
Joined: Mon 29 Oct 2007 20:47

Re: Borrelia miyamotoi

Post by Lorima » Fri 14 Dec 2012 17:39

Dorothy, I too think you should look into relapsing fever spirochetes. They are much more likely to be present in the blood, in a small sample on a slide like you have: 

Image
from Samuels and Radolf, 2010, Borrelia: Molecular Biology, Host Interaction and Pathogenesis.
US$319.00 from Amazon. :shock: Excerpts from books.google.com

There's a closely related species to B. miyamotoi called B. theileri, that was originally described in cattle in South Africa in 1903. Seems to be common there, though not yet implicated in human disease, I think. (That doesn't mean much, as they probably haven't looked, much like with B. miyamotoi in the US.) 

B. theileri seems to be almost the same as B. lonestari, found in the Lone Star tick (Amblyomma americanum) in the US. From the same Samuels and Radolf textbook:
Image

I'd look into what assays are available for relapsing fever, and what kind of RF spirochetes they are optimized for. 
Maybe this Dako Borrelia flagellin ELISA would be worth trying; 
http://www.ebiotrade.com/buyf/productsf ... 041611.htm 
It's (mostly) specific for Borrelia, but not for Bb ss or sl. If yours is a relapsing fever spirochete, that's a good thing. You could narrow down the species later, if it's positive. 
I hope this particular assay is still available. It's important that it be the whole flagellin molecule, as in this assay, not a fragment, so it will detect antibodies to any Borrelia including relapsing fever types, and not just Bbss/sl species. Then you'll have to find a lab that can run it. I wonder if a veterinary lab might be a good bet, if you can't find a human one that does this test (but you'd have to use anti-human antibody in the second step of the ELISA, not anti-cow, anti-horse, etc., to get a read-out from human serum antibodies that bind to the flagellin. Google for explanations of ELISAs and other immunoassays online and get a feel for the details of  how these assays work.) 

Here's some related info, including a quick search for spirochetes in South Africa/Africa, and serological cross-reactivity among species.  

More general information on spirochetes in Africa:
Clin Microbiol Infect. 2009 May;15(5):400-6. doi: 10.1111/j.1469-0691.2009.02819.x.
New concepts for the old challenge of African relapsing fever borreliosis.
Cutler SJ, Abdissa A, Trape JF.
Source
School of Health & Bioscience, University of East London, London, UK. s.cutler@uel.ac.uk
Abstract
Relapsing fever, caused by spirochaetes belonging to the genus Borrelia, was once the cause of worldwide epidemic disease. This was largely through infection with the louse-borne form of the disease, caused by Borrelia recurrentis (louse-borne relapsing fever (LBRF)). During the last century, we have witnessed the demise of this infection, largely owing to improved standards of living and the introduction of the insecticide DDT, resulting in a reduction in the incidence of the body louse, the vector for relapsing fever. In areas of extreme poverty this disease persists, causing a significant burden of disease. It is now looking probable that this infection is caused by a louse-adapted variant of Borrelia duttonii, transmitted by Ornithodoros moubata 'soft' ticks in East Africa. Like LBRF, infection still causes impact, particularly affecting young children and pregnant women. Over recent years, the true burden of relapsing fever caused by infection with the closely related Borrelia crocidurae, transmitted by Ornithodoros sonrai ticks, has only just begun to emerge. Here, the current state of knowledge concerning relapsing fever in Africa is reviewed.
PMID: 19489922 [PubMed - indexed for MEDLINE]
Paywall.


Thesis from 1993: 
http://eprints.ru.ac.za/4126/1/NURTON-MSc-TR93-42.pdf Free Full Text
An investigation of Borrelia burgdorferi in South Africa

Nurton, Jane Patricia (1993) An investigation of Borrelia burgdorferi in South Africa. Masters thesis, Rhodes University
3902Kb
Abstract
Four commonly occurring genera of ticks in South Africa were tested for their capacity to acquire and transmit Borrelia burgdoiferi, the causative agent of Lyme disease. Attempts were made to infect rabbits with a culture of B. burgdoiferi, and tick transmission experiments were carried out using the rabbits as the host of infection. Only one rabbit was successfully infected. Histological changes associated with a B. burgdoiferi infection were noted in this rabbit, but no spirochaetes were isolated. All other host animals failed to become infected with the B. burgdoiferi. As a consequence transmission experiments with
 the local ticks failed. Serological surveys conducted on rodents, horses and cattle using immunofluorescent and
 haemagglutination tests indicated that there is evidence that Borrelia species occur widely and that there is a possibility of B. burgdoiferi occurring in South Africa.
 Studies conducted on ticks from suspected endemic areas revealed the presence, in Ixodes bakeri only, of a spirochaete-like organism that reacted with monoclonal antibody H5332. Shortcomings of the study are highlighted and proposals are presented to address the problem of identifying specific B. burgdoiferi infections.
B. theileri was discovered, in cattle in South Africa in 1903:
Laveran A. Sur la spirillose des bovides. C R Acad Sci Paris. 1903;136:939. 

From the following paper, it sounds like B. theileri is the same as the spirochete found in the US in the Lone star tick (a hard tick). Highly related to B. miyatmotoi, also found in hard ticks. 
http://www.ncbi.nlm.nih.gov/pmc/article ... 000494.pdf http://www.ncbi.nlm.nih.gov/pmc/articles/PMC87764/ 
J Clin Microbiol. 2001 February; 39(2): 494–497.
doi:  10.1128/JCM.39.2.494-497.2001
PMCID: PMC87764
Lone Star Tick-Infecting Borreliae Are Most Closely Related to the Agent of Bovine Borreliosis
Stephen M. Rich,1 Philip M. Armstrong,2,3 Ronald D. Smith,4 and Sam R. Telford, III2,*
Author information ► Article notes ► Copyright and License information ►
This article has been cited by other articles in PMC.
Go to:
ABSTRACT
Although Borrelia theileri, the agent of bovine borreliosis, was described at the turn of the century (in 1903), its relationship with borreliae causing Lyme disease or relapsing fever remains undescribed. We tested the previously published hypothesis that spirochetes infecting Lone Star ticks (Amblyomma americanum) may comprise B. theileri by analyzing the 16S ribosomal DNAs (rDNAs) and flagellin genes of these spirochetes. B. theileri, the Amblyomma agent, and B. miyamotoi formed a natural group or clade distinct from but most closely related to that of the relapsing fever spirochetes. B. theileri and the Amblyomma agent were 97 and 98% similar at the nucleotide level within the analyzed portions of the 16S rDNA and the flagellin gene respectively, suggesting a recent divergence. The agent of bovine borreliosis might be explored as a surrogate antigen for the as-yet-uncultivatable Amblyomma agent in studies designed to explore the etiology of a Lyme disease-like infection associated with Lone Star ticks.
http://pubmedcentralcanada.ca/pmcc/arti ... 5-0033.pdf  Free full text

http://www.ncbi.nlm.nih.gov/pubmed/10376894 
Am J Vet Res. 1999 Jun;60(6):694-7.
Serologic cross-reactivity of antibodies against Borrelia theileri, Borrelia burgdorferi, and Borrelia coriaceae in cattle.
Rogers AB, Smith RD, Kakoma I.
Source
Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Illinois, Urbana 61802, USA.
Abstract
OBJECTIVE:
To evaluate the immune response induced by Borrelia theileri infection and to determine whether B theileri induces cross-reacting antibodies to other bovine borreliae.
ANIMALS:
Two 3-month-old calves, 1 of which was splenectomized.
PROCEDURE:
Calves were exposed to Boophilus microplus infected with B theileri. Rectal temperature, PCV, bacteremia, and clinical signs of infection were monitored. Serum was obtained weekly and used to evaluate the humoral response to homologous antigen and B burgdorferi and B coriaceae, using an indirect fluorescent antibody (IFA) test, and to B burgdorferi, using a commercially available ELISA. The identity of cross-reacting antigens was explored, using monoclonal antibodies to genus- and species-specific antigens in an IFA test.
RESULTS:
B theileri-infected calves produced antibodies that cross-reacted with B burgdorferi and B coriaceae whole-cell antigens. Borrelia theileri whole-cell antigen was recognized by genus-specific monoclonal antibody H9724 but not by species-specific antibody H5332. False-positive reactions were not observed when serum from B theileri-infected calves was tested by use of the ELISA for B burgdorferi.
[Note from Lorima: this means ELISA for Bb probably/maybe woudn't be positive for serum from humans with B. theileri, lonestari, or miyamotoi, either. That's why I suggested the DAKO flagellin ELISA, above] 
CONCLUSIONS:
B theileri induces humoral responses in infected cattle that can be confused with those of other borrelial infections. Care must be taken to definitively distinguish between the various borreliae that may cause disease in cattle.
CLINICAL RELEVANCE:
Serologic cross-reactivity must be taken into account when making a serodiagnosis of Lyme borreliosis or epizootic abortion in epidemiologic studies involving cattle.
PMID: 10376894 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/pubmed/2085371 
Zentralbl Bakteriol. 1990 Nov;274(2):214-26.
Antigenic cross-reactivity between Borrelia burgdorferi, Borrelia recurrentis, Treponema pallidum, and Treponema phagedenis.
Luther B, Moskophidis M.
Source
Hygienisches Institut, Medizinaluntersuchungsanstalt, Hamburg.
Abstract
The antigenic cross-reactivity between different Borrelia and Treponema species was determined by the indirect immunofluorescence antibody test and sodium dodecyl sulphate-polyacrylamide gel electrophoresis followed by immunoblotting. The protein profiles of Borrelia burgdorferi, Borrelia recurrentis, Treponema pallidum, and Treponema phagedenis revealed essential differences. Using immunoblotting, rabbit immune sera to B. burgdorferi and B. recurrentis exhibited strong cross-reactivities to heterologous borrelial antigens and, to a lesser extent, to treponemal antigens. Immune sera to T. pallidum and T. phagedenis reacted with heterologous treponemal antigens, but exhibited lesser cross-reactivities to borrelial antigens. Five B. burgdorferi and seven T. pallidum major antigens were not cross-reacting with antisera raised against T. pallidum and B. burgdorferi, respectively. However, absorption of the investigated antisera with a T. phagedenis ultrasonicate eliminated cross-reacting borrelial and treponemal antibodies.
PMID: 2085371 [PubMed - indexed for MEDLINE]

Performing your original search, spirochetes africa, in PMC will retrieve 685 records.
This is a lot of papers; I'm not able to look at all of them. 
J Clin Microbiol. 2011 Sep;49(9):3245-9. doi: 10.1128/JCM.00940-11. Epub 2011 Jul 20.
Multiplex 5' nuclease-quantitative PCR for diagnosis of relapsing fever in a large Tanzanian cohort.
Reller ME, Clemens EG, Schachterle SE, Mtove GA, Sullivan DJ, Dumler JS.
Source
Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross 624, Baltimore, MD 21205, USA. mreller1@jhmi.edu
Abstract
Relapsing fever (RF) is caused by tick- and louse-borne Borrelia spp., is characterized by recurrent fever, and is often misdiagnosed as malaria. Because of submicroscopic bacteremia, microscopy can be insensitive between febrile bouts. We designed a multiplex quantitative PCR (qPCR) assay to distinguish RF Borrelia from Plasmodium falciparum and P. vivax. The assay specifically (100%) amplified pathogenic RF Borrelia (1 copy/reaction). We then tested blood from participants within a Tanzanian cohort assessed at scheduled intervals and with fever. Among 8,617 blood samples from 2,057 participants surveyed routinely, 7 (0.08%) samples and 7 (0.3%) participants had RF DNA (median, 4.4 × 10(3) copies/ml). Of 382 samples from 310 febrile persons, 15 (3.9%) samples from 13 (4.2%) participants had RF DNA (median, 7.9 × 10(2) copies/ml). Five (1.3%) samples from 4 (1.3%) participants were found to harbor Borrelia by microscopy. We conclude that multiplex qPCR holds promise for improved clinical diagnosis and epidemiologic assessment of RF.
PMID: 21775542 [PubMed - indexed for MEDLINE] PMCID: PMC3165610 Free PMC Article

Survey in Mali for B. crocidurae (relapsing fever):
There's an image in here that looks like your images. Of course, that doesn't mean yours is B. crocidurae specifically, just that relapsing fevers, with their high blood concentrations of spirochetes, yield that kind of image. 
http://www.ncbi.nlm.nih.gov/pmc/article ... 001924.pdf  Free full text
http://www.ncbi.nlm.nih.gov/pubmed/23209863 
PLoS Negl Trop Dis. 2012 Nov;6(11):e1924. doi: 10.1371/journal.pntd.0001924. Epub 2012 Nov 29.
Endemic Foci of the Tick-Borne Relapsing Fever Spirochete Borrelia crocidurae in Mali, West Africa, and the Potential for Human Infection.
Schwan TG, Anderson JM, Lopez JE, Fischer RJ, Raffel SJ, McCoy BN, Safronetz D, Sogoba N, Maïga O, Traoré SF.
Source
Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana, United States of America.
Abstract
BACKGROUND:
Tick-borne relapsing fever spirochetes are maintained in endemic foci that involve a diversity of small mammals and argasid ticks in the genus Ornithodoros. Most epidemiological studies of tick-borne relapsing fever in West Africa caused by Borrelia crocidurae have been conducted in Senegal. The risk for humans to acquire relapsing fever in Mali is uncertain, as only a few human cases have been identified. Given the high incidence of malaria in Mali, and the potential to confuse the clinical diagnosis of these two diseases, we initiated studies to determine if there were endemic foci of relapsing fever spirochetes that could pose a risk for human infection.
METHODOLOGY/PRINCIPAL FINDINGS:
We investigated 20 villages across southern Mali for the presence of relapsing fever spirochetes. Small mammals were captured, thin blood smears were examined microscopically for spirochetes, and serum samples were tested for antibodies to relapsing fever spirochetes. Ornithodoros sonrai ticks were collected and examined for spirochetal infection. In total, 11.0% of the 663 rodents and 14.3% of the 63 shrews tested were seropositive and 2.2% of the animals had active spirochete infections when captured. In the Bandiagara region, the prevalence of infection was higher with 35% of the animals seropositive and 10% infected. Here also Ornithodoros sonrai were abundant and 17.3% of 278 individual ticks tested were infected with Borrelia crocidurae. Fifteen isolates of B. crocidurae were established and characterized by multi-locus sequence typing.
CONCLUSIONS/SIGNIFICANCE:
The potential for human tick-borne relapsing fever exists in many areas of southern Mali.
PMID: 23209863 [PubMed - in process] PMCID: PMC3510061 Free PMC Article
Images from this publication.See all images (6) Free text
Image of the spirochetes in blood:
http://www.ncbi.nlm.nih.gov/pmc/article ... 1924-g003/
"I have to understand the world, you see."
Richard Feynman

dorothy de kok
Posts: 64
Joined: Fri 2 Nov 2012 15:03

Re: Borrelia miyamotoi

Post by dorothy de kok » Fri 14 Dec 2012 19:29

Dear Lorima
What a heap of homework you have provided me with. Thanks.

I saw this earlier and tracked down the author of this thesis:
Nurton, Jane Patricia (1993) An investigation of Borrelia burgdorferi in South Africa. Masters thesis, Rhodes University
3902Kb
Unfortunately, she is now in Australia, running the science lab at a school.

But if what we are looking at is indeed RF, I have a contact at our veterinary university - Onderstepoort. He was not interested in looking into Bb (said it was too far out of his expertise), but I know he will be interested in RF. He has a special interest in tick borne infections and judging by the maps I have seen all over the net, we are a hot spot for RF. But no-one ever mentions RF. I guess our huge HIV problem is enough to deal with at this point.


The lab doing the PCR has many RF primers and are continually identifying new strains. So, I have full confidence in them. If we are fortunate enough to get positive results, the main task will be to ensure that RF diagnoses will be available to many more people here.

I was interested to read of the serious brain involvement in the other thread you bumped. It points in the RF direction as do the VERY extreme herxes while on abx. I presumed it was because of positive tests for C burnetti and Rickettsia conori that complicated the picture. One thing I am certain of - the images of the blood contain 'something' that cannot be classified as artefact.

I came across this really old article in the South African Medical Journalwhen I first started looking at the RF possibility.

https://docs.google.com/viewer?a=v&q=ca ... l7MchwCZyw

Now I am finding more old info which seems to have been forgotten:

https://docs.google.com/viewer?a=v&q=ca ... Mh-W9tX7XA

And another one from 1939:
http://webcache.googleusercontent.com/s ... clnk&gl=za

And one from 1982:
https://docs.google.com/viewer?a=v&q=ca ... fxnMbpSlHg

1944:
https://docs.google.com/viewer?a=v&q=ca ... sOXHTSEAfg

I cannot believe I did not see all these before. Unfortunately the samj.org site seems to be down at the moment, so I included google.docs links for anyone who is interested.

But now, despite all my speculations and wondering, only time and PCR will tell.



Dorothy


RitaA
Posts: 2768
Joined: Thu 1 Jul 2010 8:33

Re: Borrelia miyamotoi

Post by RitaA » Mon 11 Feb 2013 3:07

http://www.ncbi.nlm.nih.gov/pubmed/23210636
Vector Borne Zoonotic Dis. 2013 Feb;13(2):92-7. doi: 10.1089/vbz.2012.1027. Epub 2012 Dec 4.

Borrelia miyamotoi Infections among Wild Rodents Show Age and Month Independence and Correlation with Ixodes persulcatus Larval Attachment in Hokkaido, Japan.

Taylor KR, Takano A, Konnai S, Shimozuru M, Kawabata H, Tsubota T.

Source

1 Laboratory of Wildlife Biology and Medicine, Graduate School of Veterinary Medicine, Hokkaido University , Sapporo, Japan .

Abstract

Abstract To clarify how Borrelia miyamotoi is maintained in the environment in Hokkaido, we examined Ixodes persulcatus for its prevalence among wild rodents and its tick vector by detecting a portion of the borrelial flaB gene in rodent urinary bladder and blood samples, and from whole ticks. We compared B. miyamotoi infection rates to Borrelia garinii and Borrelia afzelii, which are human Lyme disease pathogens also carried by wild rodents, and which are transmitted by the same vector tick. Whereas B. garinii and B. afzelii showed age dependence of infection rates among wild rodents (18.4% and 9.9% among adults and 6.0% and 3.4% among sub-adults, respectively) when looking at urinary bladder samples, B. miyamotoi infection rates were not age dependent for either blood (4.2% among adults, and 7.9% among sub-adults) or urinary bladder samples (1.0% among adults, and 1.7% among sub-adults). Moreover, while B. garinii and B. afzelii infection rates showed increases across months (June, July [p<0.05] and August [p<0.01] had higher rates than in May for adult rodents with B. garinii, and July and August had higher rates than in May [p<0.01] for adult rodents with B. afzelii), B. miyamotoi infection rates did not show significant month dependence. These differences in month and age dependence led us to suspect that B. miyamotoi may not develop persistent infections in wild rodents, as B. garinii and B. afzelii are thought to. Furthermore, we examined the extent of rodent exposure to I. persulcatus nymphs and larvae throughout most of the tick's active season (May through September), and determined that B. miyamotoi infection rates in sub-adult rodents were correlated with larval burden (p<0.01), suggesting that larvae may be very important in transmission of B. miyamotoi to wild rodents.

PMID: 23210636 [PubMed - in process]

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