Archive for the ‘Bartonella’ Category

Case of Endocarditis Caused By Bartonella After Mitral Valve Repair

https://www.ncbi.nlm.nih.gov/pubmed/30981216

2019 Apr 13. doi: 10.1111/jocs.14047. [Epub ahead of print]

Bartonella haenselae infective endocarditis following transcatheter edge-to-edge mitral valve repair: A case report.

Nicolò F1, Scrofani R1, Antona C1.

Abstract

Infective endocarditis following a Mitraclip procedure might be an under-recognized complication. We describe the case of infective endocarditis by Bartonella henselae as a late complication in a patient with a previously implanted MitraClip system for mitral valve repair. Due to the severity of infection, surgical treatment was performed despite the high preoperative surgical risk, but recurrence of endocarditis of the biological valve implanted occurred. Although infection with Bartonella is known as a possible source of endocarditis, it has never been described before in relation to failed MitraClip therapy.

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**Comment**

A great article came out recently about Bartonella being an under appreciated public health problem:  https://madisonarealymesupportgroup.com/2019/04/24/human-bartonellosis-an-underappreciated-public-health-problem/

And, frankly, that’s an understatement!

Heart issues with Bartonella abound:  https://madisonarealymesupportgroup.com/2017/05/11/bartonella-henselae-in-children-with-congenital-heart-disease/

https://madisonarealymesupportgroup.com/2017/01/04/endocarditis-consider-bartonella/

https://madisonarealymesupportgroup.com/2018/09/28/bartonella-infective-endocarditis-with-dissemination-a-case-report-literature-review/

https://madisonarealymesupportgroup.com/2018/09/07/bartonella-infectious-endocarditis-associated-with-cryoglobulinemia-multifocal-proliferative-glomerulonephritis/

https://madisonarealymesupportgroup.com/2018/07/10/infective-endocarditis-associated-with-bartonella-henselae-a-case-series/

But many other issues abound as well:  https://madisonarealymesupportgroup.com/2019/04/09/abstract-bartonella-in-boy-with-pans/

https://madisonarealymesupportgroup.com/2019/03/21/bartonella-sudden-onset-adolescent-schizophrenia-a-case-study/

https://madisonarealymesupportgroup.com/2019/04/08/case-series-bartonella-ocular-manifestations/

https://madisonarealymesupportgroup.com/2019/03/02/skin-inflammation-nodules-letting-the-cat-out-of-the-bag/

 

Category:

Bartonella, Heart Issues, research

Human Bartonellosis: An Underappreciated Public Health Problem?

https://www.mdpi.com/2414-6366/4/2/69

Trop. Med. Infect. Dis. 2019, 4(2), 69; https://doi.org/10.3390/tropicalmed4020069

Human Bartonellosis: An Underappreciated Public Health Problem?

Mercedes A. Cheslock and Monica E. Embers *
Published: 19 April 2019
(This article belongs to the Special Issue Recent Advancements on Arthropod-Borne Infectious Diseases)

Abstract

Bartonella spp. bacteria can be found around the globe and are the causative agents of multiple human diseases. The most well-known infection is called cat-scratch disease, which causes mild lymphadenopathy and fever. As our knowledge of these bacteria grows, new presentations of the disease have been recognized, with serious manifestations. Not only has more severe disease been associated with these bacteria but also Bartonella species have been discovered in a wide range of mammals, and the pathogens’ DNA can be found in multiple vectors. This review will focus on some common mammalian reservoirs as well as the suspected vectors in relation to the disease transmission and prevalence. Understanding the complex interactions between these bacteria, their vectors, and their reservoirs, as well as the breadth of infection by Bartonella around the world will help to assess the impact of Bartonellosis on public health. View Full-Text

tropicalmed-04-00069-g001
Figure 1  The Clinical Manifestations of Bartonellosis
Excerpt from full-text
Known diseases caused by Bartonella infections include:
  • Carrion’s disease
  • cat-scratch disease
  • chronic lymphadenopathy
  • trench fever
  • chronic bacteraemia
  • culture-negative endocarditis
  • bacilliary angiomatosis
  • bacilliary peliosis
  • vasculitis
  • uveitis [1,2,4,6,7,9,10,11].
Recently, Bartonella infections have been linked to more diverse manifestations such as:
  • hallucinations
  • weight loss
  • muscle fatigue
  • partial paralysis
  • pediatric acute-onset neuropsychiatric syndrome (PANS)
  • other neurological manifestations [6,8,10].

A few case studies have also documented Bartonella in tumors, particularly vasoproliferative and those of mammary tissue [12,13,14]. The potential involvement of this pathogen in breast tumorigenesis is both disconcerting and warrants significantly more research.

Bartonella spp. are zoonotic pathogens transmitted from mammals to humans through a variety of insect vectors including the sand fly, cat fleas, and human body louse [4,5]. New evidence suggests that ticks, red ants, and spiders can also transmit Bartonella [15,16,17,18]. Bed bugs have been implicated in the transmission cycle of B. quintana and have been artificially infected [19]. B. quintana was found in bed bug feces for up to 18 days postinfection [19]. The diversity of newly discovered Bartonella species, the large number and ecologically diverse animal reservoir hosts, and the large spectrum of arthropod vectors that can transmit these bacteria among animals and humans are major causes for public health concern.

Regarding ticks….

3.2. Arachnids (Spiders and Ticks)

Over the last 10 years, the topic of ticks transmitting Bartonella species has been widely debated. Evidence exists to support the transmission of Bartonella through many different species of ticks.

Ixodid ticks, also known as hard ticks, appear to be the main type of tick associated with these bacteria. Tick cell lines have been used to show that Bartonella can replicate and survive within:

  • Amblyoma americanum (Lone Star Tick)
  • Rhipicephalus sanguineus (Brown Dog Tick)
  • Ixodes scapularis cells [77] (Deer Tick)

In California, questing ticks of

  • Ixodes pacificus (Western Black legged Tick)
  • Dermacentor occidentalis (Pacific Coast Tick)
  • Dermacentor variabilis (American Dog Tick)

were collected when in the adult and nymphal stages and tested for Bartonella by PCR for the citrate synthase gene. [78]. All types of ticks were found to contain Bartonella DNA, although in varying percentages and locations. These data alone do not prove that ticks can transmit Bartonella spp. Bacteria; however, the results do show Bartonella DNA occurring naturally in these wild ticks.

In Palestine,

  • Hyalomma spp. (Genus of hard-bodied tick) found in Asia, Europe, & North and South Africa.
  • Haemphysalis spp. (The Asian Long-horned tick is an example)
  • Rhipicephalusspp. (Hard-bodied tick native to tropical Africa)

ticks were collected from domestic animals and tested by PCR for the Bartonella intergenic transcribed spacer (ITS) region [38]. These ticks were infected with 4 strains of Bartonella: B. rochalimae, B. chomelii, B. bovis, and B. koehlerae [38]. While this study tested a collection of ticks found on domestic animals, the results suggest that individuals in close contact with these animals should be aware of the potential for transmission through tick bites.

In a sampling of ticks (Ixodes scapularis and Dermacentor variabilis) and rodents (Peromyscus leucopus) from southern Indiana, the midgut contents of the tick species and rodent blood were analyzed by 16S sequencing. Bartonella was present in a moderate percentage (26% in D. variabilis and 13.3% in I. scapularis) of larvae and nymphs of both tick species, even those scored as unengorged, but was present in the majority (97.8%) of the rodents tested [79].
A survey of ticks from 16 states in the U.S. revealed that the overall prevalence of Bartonella henselae in Ixodes ticks was 2.5% [80].
Interestingly, the highest rate of both Borrelia spp. (63.2%) and B. henselae (10.3%) was found in Ixodes affinis ticks collected from North Carolina.
Ixodes ricinus has been the focus of studies that support tick transmission of Bartonella spp. in Europe. This is because I. ricinus is an important vector for tick-borne diseases in Europe [81]. I. ricinus have been collected in the larval, nymphal, and adult stages in Austria [82]. The analyses revealed that 2.1% of all ticks were infected with Bartonella spp., with the highest rate in ticks derived from Vienna (with a 7.5% infection rate), and that adult ticks had a higher prevalence than other stages [82].
B. henselae, B. doshiae, and B. grahamii DNA were amplified, and this was the first study to find Bartonella-infected ticks in Austria [82].
A recent One Health perspective review on Bartonella indicated that the overall presence of Bartonella in ticks (combining evidence from multiple surveillance studies) was approx. 15% [83].
B. henselae DNA has also been isolated from I. ricinus removed from an infected cat. However, whether the cat gave the tick Bartonella or vice versa cannot be established, so the vector competence of these ticks for transmission cannot be determined [30].
A lab in France has studied the relationship between I. ricinus and Bartonella transmission. One study focused on the ability of ticks to maintain infection from one life stage to the next and tested a vertical transmission from adults to eggs. The authors used B. henselae and found that a transstadial transmission was possible and that a transovarial transmission was not likely [84]. The researchers also supplied evidence to support the vector competency of I. ricinus by amplifying B. henselae DNA from the salivary glands of infected ticks and by amplifying DNA from blood 72 h after infected ticks fed through an artificial system [84]. Although the evidence strongly suggests the ability of ticks to transmit these bacteria, the system employed artificial means for feeding; therefore, one major critique has been that it is not representative of a natural blood meal from a host.
To address this issue, another experiment was performed to the assess vector competency of I. ricinus to transmit Bartonella birtlesii [85]. Mice were infected with B. birtlesii through an intravenous injection via a tail vein, and once mice were infected, naïve ticks were fed on the mice and kept for 3 months to molt. Nymphal ticks were shown to transmit B. birtlesii to naïve mice, and adult ticks were shown to infect blood through a feeder method [85]. B. birtlesii was identified in the blood of the recipient mice through PCR and immunofluorescence [85]. This evidence strongly supports the transmission of these bacteria by ticks. However, the limitation is that this only supports I. ricinus’ ability to transmit a very specific strain of Bartonella, B. birtlesii, which is not linked to human disease.
Concerns such as these related to vector competence and transmission can only be quelled by repeated studies utilizing multiple strains of Bartonella and differing tick species.
An interesting case study provided evidence of spiders transmitting Bartonella. A mother and two sons suffered from neurological symptoms following bites suspected from woodlouse hunter spiders [18]. Bartonella henselae DNA was amplified from the blood of the family as well as from a woodlouse and a woodlouse hunter spider near the family’s home [18]. It cannot be determined if the family contracted the bacteria from the woodlouse or the woodlouse hunter spider or if the lice and spiders contracted the bacteria from the family. This case study points to the importance for diagnosticians to test for bacterial infections after suspected arachnid bites. It also emphasizes the lack of knowledge on the possible vectors that transmit Bartonella as well as the range of manifestations by infection with Bartonella.

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**Comment**

I think we can safely state that Bartonella IS an under appreciated health problem.

 

 

Category:

Bartonella, Eye Issues, Heart Issues, Psychological Aspects, research, Ticks

Tick Data – 76% Infected With One Organism, 20% Have Three or More Pathogens

https://www.tickcheck.com/statistics?

Each tick submitted for testing contributes to the research being conducted at TickCheck. By keeping records of all the results generated, we have been able to gain valuable insights into disease prevalence and co-infection rates. The comprehensive testing panel has been especially helpful in contributing to this research by ensuring all diseases and coinfections are accounted for when examining a tick.

Our current research shows:
  • 76% of ticks tested have at least one disease causing organism
  • 49% are co-infected with two or more organisms
  • 20% carry three or more
  • 9% of the ticks tested carry four or more

Infection Visualization by Tick Species

All Ticks Tested
76% Positive for Infection
Negative (24%)
_____________________________
  • 93% Positive for Infection
  • Negative (7%)
  • 63% Positive for Infection
  • Negative (37%)
  • 48% Positive for Infection
  • Negative (52%)

Coinfection Visualization

  • 2+ coinfection 49%
  • No coinfection 51%

Pathogenic Prevalence

The information below shows the positive/negative prevalence ratio of selected pathogens we test for. These pathogens were observed in ticks from the United States and Canada. Data set includes tests performed since TickCheck’s founding in 2014 and is updated in real time. (

Go to link at beginning to filter by state.  I’ve added the 3 listed for Wisconsin next to the entire sample size.  Please note the small sample sizes of WI ticks. 

Borrelia burgdorferi (deer tick) associated with Lyme disease

Sample size of 3,280 ticks.           70 Wisconsin ticks
  • 30% postive                                           33% positive
  • 70% negative                                         67% negative

Borrelia burgdorferi (western blacklegged tick) associated with Lyme disease

Sample size of 279 ticks.
  • 4% positive
  • 96% negative

Borrelia burgdorferi (lone star tick) associated with Lyme disease

Sample size of 899 ticks.
  • 8% positive
  • 92% negative

Borrelia burgdorferi (American dog tick) associated with Lyme disease

Sample size of 901 ticks.
  • 2% positive
  • 98% negative

Anaplasma phagocytophilum associated with anaplasmosis

Sample size of 2,146 ticks.           36 Wisconsin ticks
  • 8% positive                                           11% positive in Wisconsin
  • 92% negative                                        89% negative in Wisconsin

Babesia microti associated with babesiosis

Sample size of 1,894 ticks.           32 Wisconsin ticks
  • 4% positive                                            6% positive
  • 96% negative                                        94% negative

Bartonella spp. associated with bartonellosis

Sample size of 1,060 ticks.
  • 47% positive
  • 53% negative

Ehrlichia chaffeensis associated with ehrlichiosis

Sample size of 857 ticks.
  • 2% positive
  • 98% negative

Rickettsia spp. associated with Rocky Mountain spotted fever

Sample size of 944 ticks.
  • 23% postive
  • 77% negative

Francisella tularensis associated with tularemia

Sample size of 1,028 ticks.
  • 1% positive
  • 99% negative

Borrelia miyamotoi associated with B. miyamotoi

Sample size of 1,091 ticks.
  • 6% postive
  • 94% negative

Borrelia lonestari associated with STARI

Sample size of 831 ticks.
  • 19% postitive
  • 81% negative

Babesia spp. associated with babesiosis

Sample size of 564 ticks.
  • 5% positive
  • 95% negative

Mycoplasma spp. associated with Mycoplasma spp.

Sample size of 948 ticks.
  • 8% positive
  • 92% negative

Borrelia spp. associated with Borrelia spp.

Sample size of 612 ticks.
  • 17% postive
  • 83% negative

Powassan virus Lineage II associated with Deer tick virus

Sample size of 102 ticks.
  • 24% positive
  • 76% negative

Borrelia mayonii associated with Lyme disease

Sample size of 376 ticks.
  • 100% negative

Ehrlichia ewingii associated with ehrlichiosis

Sample size of 283 ticks.
  • 100% negative

Rickettsia amblyommii associated with Rocky Mountain spotted fever

Sample size of 177 ticks.
  • 46% positive
  • 54% negative

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For more about Tickcheck: https://www.tickcheck.com/about

You can request free tick identification by sending in a quality picture of your tick. Using real-time PCR (Polymerase Chain Reaction), Tickcheck can determine the presence of certain pathogens with an accuracy level of over 99.9%.  All information about how to send in your tick, costs of various tests, time for results, etc. is found here:  https://www.tickcheck.com/info/faq

Jonathan Weber is the founder and CEO of TickCheck and became acutely aware of the dangers of tick-borne diseases after his father caught Lyme during a family trip on the Appalachian Trail.

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**Comment**

This information supports current research showing many patients are infected with numerous pathogens causing more severe illness & requiring far more than the CDC’s mono therapy of doxycycline:  https://madisonarealymesupportgroup.com/2018/10/30/study-shows-lyme-msids-patients-infected-with-many-pathogens-and-explains-why-we-are-so-sick/

It also supports previous work showing coinfections within ticks:  https://madisonarealymesupportgroup.com/2017/05/01/co-infection-of-ticks-the-rule-rather-than-the-exception/

What I want to know is WHY nothing’s being done about this?  Why are people STILL given 21 days of doxycycline when that particular med will not work on numerous pathogens?
Lastly, a word about statistics – this tick data should be used with caution & never to turn sick patients away due to a statistic. If you are the sorry sucker who gets bit by that ONE tick carrying a “statistically insignificant” pathogen, you still got bit and have to deal with it.  
Shame on doctors for turning sick people away due to statistics and maps.
There’s no such thing as an “insignificant” tick bite!

But, Patients are STILL being turned away:  https://madisonarealymesupportgroup.com/2019/04/22/its-just-crazy-why-is-lyme-disease-treatment-so-difficult-to-find-in-mississippi/

https://madisonarealymesupportgroup.com/2019/03/19/jacksonville-family-shares-daughters-9-month-diagnosis-of-rare-disease-which-isnt-rare-lyme/

https://madisonarealymesupportgroup.com/2018/05/31/no-lyme-in-the-south-guess-again/

https://madisonarealymesupportgroup.com/2017/10/24/no-lyme-in-oklahoma-yeah-right/

https://madisonarealymesupportgroup.com/2016/09/24/arkansas-kids-denied-lyme-treatment/  “They had the classic symptoms, they had the bulls eye rash, they had the joint pain, they had fevers and had flu like symptoms, yet we were denied treatment for at least two of them and I don’t understand how this is legal,” said Bowerman.

According to Dr. Naveen Patil, Director of the Infectious Disease Program, ADH,

“We don’t have Lyme Disease in Arkansas, we have the ticks that transmit Lyme Disease but we don’t have any recorded cases of Lyme Disease.” 

Bowerman also received a letter from the clinic stating doctors would no longer treat her children because she consistently questioned their medical advice and recommendations.

This is getting to be way beyond ludicrous.

 

Category:

Anaplasmosis, Babesia, Bartonella, Borrelia Miyamotoi (Relapsing Fever Group), Ehrlichiosis, Lyme, Mycoplasma, research, Rickettsia, Rocky Mountain Spotted Fever, Testing, Ticks, Tularemia, Viruses

First report of Bartonella Culturing and MLST-based Genotyping From Blood in Southeast European Cat Living With Patient With Bartonella

https://www.ncbi.nlm.nih.gov/m/pubmed/30940084/

First isolation and genotyping of Bartonella henselae from a cat living with a patient with cat scratch disease in Southeast Europe.

Stepanić M, et al. BMC Infect Dis. 2019.

Abstract

BACKGROUND: The bacterial genus Bartonella is distributed worldwide and poses a public health risk. Cat-scratch disease caused by B. henselae in Croatia was first described in 1957. It is present throughout the country: a survey of serum samples from 268 Croatian patients with lymphadenopathy showed that 37.7% had IgG antibodies. Despite this prevalence, we are unaware of reports of Bartonella culturing from infected humans or cats in Croatia or elsewhere in southeast Europe.

CASE PRESENTATION: Here we describe the diagnosis of a 12-year-old child with lymphadenopathy in Croatia with cat-scratch disease based on antibody detection and clinical signs, and the subsequent culturing and genotyping of B.henselae from the cat’s blood. The B. henselae isolate was grown on different blood agar plates and its identity was confirmed based on polymerase chain reaction (PCR) amplification of 16S ribosomal deoxyribonucleic acid (16S rDNA) and sequencing. Multi-locus sequence typing (MLST) identified the strain genotype as sequence type 5, commonly found zoonotic B. henselae strain in cats. The child recovered after azithromycin therapy, and B. henselae in the cat was eliminated within three months after doxycycline treatment.

CONCLUSIONS: This is, to our knowledge, the first report of B. henselae culturing and MLST-based genotyping from cat’s blood in southeast Europe. Our ability to detect B. henselae in blood through culturing but not PCR suggests that the prevalence of infected cats with low bacteremia is very high, suggesting the need to develop faster, more sensitive detection assays.

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**Comment**

Bartonella is everywhere and finally getting the press it deserves. Nearly every Lyme/MSIDS patient I know has it yet the U.S. is in denial. 

Perfectly healthy people can become infected without any cat exposure:

 https://madisonarealymesupportgroup.com/2019/01/23/chest-imaging-of-cat-scratch-disease-in-2-year-old-immunocompetent-baby-with-no-history-of-cat-contact/

https://madisonarealymesupportgroup.com/2018/07/10/bartonella-henselae-neuroretinitis-in-patients-without-cat-scratch  All the patients denied a history of a cat or any animal contact, or of having CSD findings.

https://madisonarealymesupportgroup.com/2018/07/05/cat-scratch-disease-in-a-1-5-year-old-girl-case-report/  Healthy 1.5-year-old girl who was seen in hospital for the sparing use of her left arm when crawling. Tested positively for Bartonella henselae.

https://madisonarealymesupportgroup.com/2018/04/03/encephalopathy-in-adult-with-cat-scratch-disease/  Case of a 53-year-old healthy man, presenting with confusion. Serology confirmed Bartonella henselae infection.

https://madisonarealymesupportgroup.com/2019/01/09/transverse-myelitis-guillain-barre-associated-with-bartonella/  Healthy 10 year old girl had coexisting transverse myelitis and Guillain-Barré syndrome (GBS) related to infection with Bartonella henselae.

https://madisonarealymesupportgroup.com/2018/11/05/skull-infection-due-to-bartonella/  While cats are implicated, this 3 year old had no significant medical history, presented at emergency department for a 2-week history of worsening scalp lump with redness.

https://madisonarealymesupportgroup.com/2018/03/04/bartonella-erythema-nodosum-atypical-presentations/  All immunocompetent hosts.

Lastly, this article points out the importance of utilizing blood culture vs PCR for Bartonella.  PCR tests require much less time, less skill to interpret the results, less waste, which all culminate to less cost; however, as you can see from the last item in the list, traditional culture method (TCM) beats out PCR in the area of rare and emerging pathogens.  List below derived from this:  https://instantlabs.com/traditional-culture-methods-or-pcr-which-is-right-for-you/

Differences between TCM & PCR testing:

    • Skill Level Required: Knowing what to look for can be tough when it comes to traditional culture method TCM. While some tests are cut and dry — the organism either grew up or it didn’t — others require a bit of interpretation in order to be correctly read. Bacterial identification is an art form that can take years to perfect. This translates out into higher wages and more skill required for TCM.
    • Time to Result: Bacteria grow on their own schedule. More time spent waiting typically means more cost for TCM.
    • Accuracy: There’s always one oddball out in a crowd, and bacteria are no different. There’s always one cell that just won’t conform to the standardized norm for a species. Because many of the traits that TCM look for are considered non-essential traits by the organism in question, there’s always the possibility that a pathogenic organism could be missed even by the most seasoned technician.
    • Waste Generated: At first glance, the amount of waste each test generates per sample doesn’t seem like an important concern, but it is. Consider this: each pound of waste generated has to be disposed of properly. And because TCM often require both the primary and secondary enrichment to be plated in replicates of 5, all of those plates add up to quite the pile.
    • Cost: It’s not just the cost of reagents that needs to be considered. The longer time required for TCM keeps staff from doing other important tasks, and the differences in the amount of reagents needed. Sure, a single plate may cost only $0.25, but when you’re going through 24 at a time, that can add up quickly.
    • Diversity of Available Tests: This is where TCM beats out Real-Time PCR. There are still some very rare and emerging pathogens where Real-Time PCR tests don’t yet exist – at least not commercially available and approved versions. For these very rare pathogens, TCM is still the method of choice.

There has been a concerted suppression of microscopy for Lyme/MSIDS:  https://madisonarealymesupportgroup.com/2017/12/13/suppression-of-microscopy-for-lyme-diagnostics-professor-laane/

https://madisonarealymesupportgroup.com/2018/05/15/news-release-on-57-1-million-lyme-disease-lawsuit-filed-against-cdc/

This article also reveals how Lida Mattman’s Gold Standard Culture Method has disappeared thanks to this concerted suppression on microscopy.  https://madisonarealymesupportgroup.com/2019/04/02/transmission-of-lyme-disease-lida-mattman-phd/

Could it be that folks sitting on the CDC/NIH/IDSA boards have patents on testing?  YEP! ConflictReport

It is high time authorities allow & promote direct testing for Lyme/MSIDS.

 

Category:

Bartonella, research, Testing, Treatment

CEO of Galaxy Diagnostics: ‘Important Research is Emerging That Implicates a Range of Fastidious, Low-level Infections in Complex Immunological Disease processes’

https://www.galaxydx.com/galaxys-president-amanda-elam-reflects-on-decade/

Amanda Elam, President and CEO of Galaxy Diagnostics, Reflects on the Past 10 Years

Amanda-headshot-298x300

Amanda Elam, President & CEO of Galaxy Diagnostics


Ten years ago, I joined the Galaxy Diagnostics founding team to make the BAPGM testingtechnology and Bartonella ePCR™ available for clinical and research use in both animal and human medicine.

After over a decade in research on entrepreneurship and innovation and multiple start-up experiences, I was excited to organize and launch a high-technology company in healthcare.

Healthcare is a complicated industry and marketplace with multiple layers of highly bureaucratic regulatory structures and multiple stakeholders, including patients, practitioners, government and third-party regulators, professional societies, medical boards, guideline writers, researchers, insurance providers, health IT providers, patient advocates, and more. Consequently, resistance to change is strong in healthcare and medicine.

As an experienced entrepreneur and a completely nerdy organizational sociologist, I was thrilled with the opportunity to work with my co-founders on this new, innovative start-up. While the lessons in entrepreneurship and medical innovation, to date, have been hard won, the positive impact on patient outcomes has been thrilling.

So, what did I learn?

Commercialization of New Tests is Hard

The hardest lesson I have learned as a Galaxy leader these last 10 years is how unbelievably difficult it is to commercialize a new medical technology. For diagnostic labs, there are four main challenges to commercializing new tests:

  1. Laboratory regulations change continuously, which dramatically increases the costs of doing business and introduces a lot of uncertainty into the odds of maintaining a sustainable business model.
  2. Medical guidelines lag behind new discoveries and raise the accepted standards for clinical evidence.
  3. Pricing standards and insurance reimbursements do not support an early-stage business model, but are instead based on high volumes of established medical tests run by very large companies.
  4. Access to patient samples and funding for clinical validation are both limited, especially in areas of new discovery and small patient populations.

Wait, wait—there’s more.

Investors will fund commercialization activities that lead quickly to revenue but are reluctant to fund the clinical research required to translate clinical tools into the marketplace. New labs are left with the enormous task of raising grant funding or bootstrapping the research studies needed for commercialization. Many never bother.

This reality places a tremendous burden on conscientious founders to make personal and financial sacrifices to commercialize new technologies “the right way” (with research and publication). In the case of emerging medical discoveries, like those surrounding tick-borne disease, founders are responsible for building markets for new technologies through healthcare provider education, often amid the highly contested terrain of expert medical opinion and patient advocacy.

Thank goodness for the NIH SBIR program, our local North Carolina Biotechnology Center, our corporate partners at Bayer Healthcare, IDEXX, the One Health Commission, our research collaborators, and our early stage investors. It is through these relationships that we have been able to cobble together the resources required to move our science, technology, and commercial offerings forward to the direct benefit of patients.

Disease vs. Infection

The most surprising lesson that I have learned from my Galaxy experience is that, from a clinical standpoint, disease and infection are two different things. A person can be infected with a pathogen, but that does not mean s/he will get sick, even if there is a disease associated with that pathogen. In other words, you can be infected, or more precisely “colonized,” with a pathogen and not show symptoms. These types of infections are sometimes referred to as subclinical or latent.

Biology is complex. Our bodies are made up of billions of microbes; some are beneficial, some are pathogenic, and others are opportunistic (only a problem under the certain conditions). In the world of infectious disease, disease is caused primarily by the host’s response to the infection (i.e., immune response). And, despite all the significant advances in medicine over the past century, we still don’t actually know what causes many well-known diseases.

In fact, scientists are still making discoveries about how the body works, including recent discoveries suggesting that blood is not sterile (especially not in sick people and animals), that a lymphatic vasculature provides a pathway between the bloodstream and the central nervous system, and most recently showing vascular structures in bone.

In the field of emerging infectious disease, important research is emerging that implicates a range of fastidious, low-level infections in complex immunological disease processes, including Bartonella species, Borrelia species, and other vector-borne infections. Concepts like stealth infection and the pathobiome are helpful as researchers try to sort out these questions, but progress is very slow and hampered by the lack of research funding for chronic infectious disease. To complicate things further, our bodies are complex biological systems with only a few ways to express disorder and disease, leaving our doctors with the challenging task of figuring out which of a long list of potential causal and complicating factors could be involved.

Science Cannot Prove Everything

In my well-considered opinion, the most surprising assumption dominating medicine today is that doctors should only practice what science has proven. Unfortunately, people and animals will get sick with diseases that we may not know about at all. While much of the controversy related to the role of infection in chronic disease could be addressed by research on chronic disease, not every clinical question can be answered even by the most rigorous research designs (e.g., prospective, controlled experimental designs), especially where new discoveries are concerned.

Disease is an organic process. Simply defining a sample population can be challenging in diagnostics research. How do you design a study to determine the clinical utility of a new test if the symptoms are non-specific and potentially caused by myriad factors, or if they only appear in some people with the disease? In the case of bartonellosis, most studies have focused on patients with suspected cat scratch disease (e.g., persistent swollen lymph nodes and contact with cats). However, persistent swollen lymph nodes can be caused by other infections and by blood cancers. Research from NCSU and other Bartonella research teams around the world further suggest that atypical presentations of cat scratch disease (Bartonella henselae infection) are much more common than previously recognized.

We see similar issues in research on borreliosis. For instance, most diagnostic studies have focused on individuals with a bullseye rash, when only 50% or fewer of acute infections present with this nebulous clinical sign. Study methodologies and subsequent findings are limited when new diagnostics are tested only on patient groups with specific symptoms and compared with prior diagnostic methods.

Clinical utility demands better research designs that include patients with typical and atypical signs as well as healthy controls.

One Health and a New Frontier of Medicine

In my opinion, we are now on the verge of a whole new frontier of medicine — the infectious etiology of chronic disease. This area of medical discovery is a central point of interest in the global One Health movement, which includes researchers around the world focusing on the intersection of human, animal, and environmental health.

To better address the challenges of substantiating new medical discoveries and translating new diagnostic and therapeutic tools into clinical practice, we have to work together to identify disease risks and to educate medical practitioners, patients, disease advocates, public health authorities, and the general public on the emerging science.

As a sometime patient myself, I want my doctor to have the access to the latest research and diagnostic tools, not just medical guidelines based on decades-old science. We all have to recognize the complexity of chronic illnesses and be open to understanding the role that multiple factors, from immune function to infection, potentially play in each individual case of chronic illness. We also have to recognize that due to our complex biology, current technical limitations, and highly competitive funding priorities, science cannot answer every clinical question today.

Yet doctors still seek to provide individualized care and patients still want the best that science and medicine can offer to solve their problems today. Somehow, some way, we have to find the means to provide patients with the best possible care today while moving new medical discoveries forward in a landscape that is very inhospitable to medical innovation and clinical translation.

References

Bhattacharyya, M. et al. (2017). The conserved phylogeny of blood microbiome. Molecular Phylogenetics and Evolution, 109, 404-408. doi:10.1016/j.ympev.2017.02.001 https://www.ncbi.nlm.nih.gov/pubmed/28216014

Potgieter, M. et al. (2015). The dormant blood microbiome in chronic, inflammatory diseases. FEMS Microbiology Reviews, 39(4), 567-591. doi:10.1093/femsre/fuv013 https://www.ncbi.nlm.nih.gov/pubmed/25940667

Davenport, A. C. et al. (2013). Phylogenetic diversity of bacteria isolated from sick dogs using the BAPGM enrichment culture platform. Journal of Veterinary Internal Medicine, 27(4), 854-861. doi:10.1111/jvim.12094 https://www.ncbi.nlm.nih.gov/pubmed/23647339

Raper, D. et al. (2016). How do meningeal lymphatic vessels drain the CNS? Trends in Neurosciences, 39(9), 581-586. doi:10.106/j.tins.2016.07.001 https://www.ncbi.nlm.nih.gov/pubmed/27460561

Louveau, A. et al. (2015). Structural and functional features of central nervous system lymphatic vessels. Nature, 523(7560), 337-341. doi:10.1038/nature14432 https://www.ncbi.nlm.nih.gov/pubmed/26030524

Ben-Tekaya, H. et al. (2013). Bartonella and Brucella – Weapons and strategies for stealth attack. Cold Spring Harbor Perspectives in Medicine, 3(8), a010231. doi:10.1101/cshperspect.a010231 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3721268/

Vayssier-Taussat, M. et al. (2015). Emerging horizons for tick-borne pathogens: From the ‘one pathogen-one disease’ vision to the pathobiome paradigm. Future Microbiology, 10(12), 2033-2043. doi:10.2217/fmb.15.114 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4944395/

Cochran, G. M. et al. (2000). Infectious causation of disease: An evolutionary perspective. Perspectives in Biology and Medicine, 43(3), 406-448. doi:10.1353/pbm.2000.0016 http://muse.jhu.edu/article/25974

Nelson, C. A. et al. (2018). Cat scratch disease: U.S. clinicians’ experience and knowledge. Zoonoses and Public Health, 65(1), 67-73. doi:10.1111/zph.12368 https://www.ncbi.nlm.nih.gov/pubmed/28707827

Breitschwerdt, E. B. (2017). Bartonellosis, One Health and all creatures great and small. Veterinary Dermatology, 28(1), 96-e21. doi:10.1111/vde.12413 https://www.ncbi.nlm.nih.gov/pubmed/28133871

Regier, Y. et al. (2016). Bartonella spp. – A chance to establish One Health concepts in veterinary and human medicine. Parasites & Vectors, 9(1), 261. doi:10.1186/s13071-016-1546-x https://www.ncbi.nlm.nih.gov/pubmed/27161111

Steere, A. C. et al. (2016). Lyme borreliosis. Nature Reviews. Disease Primers, 2, 16090. doi:10.1038/nrdp.2016.90 https://www.ncbi.nlm.nih.gov/pubmed/27976670

Garg, K. et al. (2018). Evaluating polymicrobial immune responses in patients suffering from tick-borne diseases. Scientific Reports, 8, 15932. doi:10.1038/s41598-018-34393-9 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6206025/

O’Connor, S. M. et al. (2006). Emerging infectious determinants of chronic diseases. Emerging Infectious Diseases, 12(7), 1051-1057. doi:10.32-1/eid1207.060037 https://www.ncbi.nlm.nih.gov/pubmed/16836820

North Carolina State University. (2012). 7th international conference on Bartonella as animal and human pathogens. Retrieved from the NC State YouTube channel at https://www.youtube.com/watch?v=uZImyyRzi70

 

 

 

 

 

Category:

Activism, Bartonella, Lyme, research