Treatment of infective endocarditis (IE) should be initiated promptly. This might hamper the chances to identify the causative organism in blood cultures. Microbiological sampling of infected valve in patients undergoing surgery might identify the causative organism. The impact of pre-operative antimicrobial treatment on the yield of valve samples is not known. This study evaluated the impact of the duration of the pre-operative antibiotic treatment on valve culture and 16S rRNA PCR findings from resected endocardial samples. Patients meeting the modified Duke criteria of definite or possible IE and undergoing valve surgery due to IE during 2011-2016 were included from Southern Finland. Eighty-seven patients were included.
In patients with shorter than 2 weeks of pre-operative antimicrobial treatment, PCR was positive in 91% (n = 42/46) and valve culture in 41% (n = 19/46) of cases. However, in patients who had 2 weeks or longer therapy before operation, PCR was positive in 53% (n = 18/34) and all valve cultures were negative. In 14% of patients, PCR had a diagnostic impact. In blood-culture negative cases (n = 13), PCR could detect the causative organism in ten patients (77%). These included five cases of Bartonella quintana, one Tropheryma whipplei, and one Coxiella burnetii. Long pre-operative antimicrobial treatment was shown to have a negative impact on microbiological tests done on resected endocardial material. After 2 weeks of therapy, all valve cultures were negative, but PCR was positive in half of the cases. PCR aided in diagnostic work-up, especially in blood culture negative cases.
The dilemma “to treat or not to treat” because of hampered ability to subsequently test for organisms is real; however, the risk for not treating is potentially death.
The big point for Lyme/MSIDS patients; however, is the fact they found Bartonella and Coxiella burnettii, also known as Q-fever in patients with infective carditis.
https://www.columbia-lyme.org/q-fever Those working with farm animals are at greater risk through inhalation or ingestion of soil or animal waste particles; however, ticks do transmit it.
Signs and Symptoms
Symptoms include high fever, headache, sore throat, malaise, nausea, diarrhea, chest pain, nonproductive cough, pneumonia, and hepatitis. Neurological manifestations occur in about one percent of patients and could develop into meningitis, encephalitis, myelitis and/or peripheral neuropathy. Endocarditis, infection of the heart valves, is the most serious manifestation. However, it is usually found in patients with preexisting valvular disease. Unfortunately, the mortality rate is increasingly high, currently at 65 percent.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC88923/ Interestingly, even as far back as the 30’s, Q fever was noted to have properties of both viruses and rickettsiae. This document states Q fever may occur in patients without any animal contact due to it’s ability to be spread by wind. The same document states human Q fever cases have occurred in the following:
An OB after an abortion on an infected woman
sexually in infected mice
possibly from infected dogs
The real kicker on that last one was the 1984 report of 13 people who developed febrile respiratory disease by playing poker in a room where a cat had delivered kittens. Abstract here:
Kosatsky T. Household outbreak of Q-fever pneumonia related to a parturient cat. Lancet. 1984;ii:1447–1449. [PubMed]
bradycardia (slow heart rate)
palatal petechiae (red or purple spots on mouth palate)
rapidly enlarging bilateral pulmonary infiltrates (fluid in both lungs)
Overall, 129/929 (13.9%) Ixodes ticks were PCR positive for Borrelia burgdorferi sensu stricto, 48/929 (5.1%) for B. bissettiae whereas 23/929 (2.5%) were PCR positive for a Bartonella henselae. Borrelia bissettiae or B. burgdorferi s.s. and B. henselaeco-infections were found in I. affinis from North Carolina at a rate of 4.5%; in a single I. scapularis from Minnesota, but not in I. pacificus. For both bacterial genera, PCR positive rates were highly variable depending on geographic location and tick species, with Ixodes affinis (n = 155) collected from North Carolina, being the tick species with the highest prevalence’s for both Borrelia spp. (63.2%) and B. henselae (10.3%). Based on the results of this and other published studies, improved understanding of theenzootic cycle, transmission dynamics, and vector competence of Ixodes species (especially I. affinis) for transmission of Borrelia spp. and B. henselae should be a public health research priority.
One of the most understated studies yet. Research on transmission and vector competence is screaming to be done – especially for Bartonella as mainstream medicine still thinks it’s a simple disease caused by the scratch of a cat that only affects immunocompromised people. They also insist the black-legged tick is the sole perp for Lyme. Both of these tenets are being shattered on a daily basis.
Two ticks species known to be transmitters of disease (I. affinis and I. minor)were transported into Canada and are actually moreimportant vectors of Bbsl in the southeastern U.S. than the blacklegged tick.
THESE FINDINGS UNDERSCORE THE FACT PEOPLE DO NOT HAVE TO GO AN ENDEMIC AREA TO CONTRACT LYME DISEASE AND ASSOCIATED TICK-BORNE DISEASES.
HONOLULU (HawaiiNewsNow) – A new University of Hawaii study shows Hawaii keiki are more than three times more likely to get severe forms of cat scratch disease than mainland kids.
“It’s caused by a bacteria that you primarily get from cats that you get through a scratch or a bite and it’s transmitted to cats by fleas,” said Dr. Scarlett Johnson, a UH pediatric resident.
Symptoms include fever and swollen lymph nodes. UH and Kapiolani Medical Center doctors studied 18 children who got severe reactions.
“These were children who had infections of their spleen, liver, meningitis, encephalitis. involvement of their eye. Some even developed bone lesions so it was a significant illness in these children,” said Dr. Jessica Kosut, a pediatric hospitalist.
Sarah Pacheco got a mild form of the illness years ago when her new kitten, Kipling, scratched her arm.
“I had just gotten a kitten and they play and you are bound to get scratched, but I noticed I lost my voice completely,” she said.
Cat scratch disease is still rare. Doctors think Hawaii’s humid climate, outdoor lifestyle and higher feral cat population could be partly to blame.
“I don’t think it’s cats that are in people’s homes, but it can be, but a couple of the children that we took care of described playing with cats that were out in the neighborhood and one child was hiding cats in his closet to keep them a secret from his mother,” said Dr. Kosut.
Doctors say cat scratch disease is treatable. Just make sure your cat doesn’t have fleas and doesn’t play with feral cats, and you don’t have to kick out your kitty.
“I’m definitely a fan of cats and I wouldn’t say that this should discourage anyone from getting cats or adopting cats. I just want providers to be aware of it,” said Dr. Johnson.
Cat Scratch Disease (CSD) or Bartonella IS NOT RARE! And while some develop fever and swollen lymph nodes, it presents in a million different ways – some purely psychological.
And cats aren’t the only things transmitting it.
http://townsendletter.com/July2015/bartonellosis0715_3.html Mode of Transmission: Arthropod vectors including fleas and flea feces, biting flies such as sand flies and horn flies, the human body louse, mosquitoes, and ticks; through bites and scratches of reservoir hosts; and potentially from needles and syringes in the drug addicted. Needle stick transmission to veterinarians has been reported. There is documentation that cats have received it through blood transfusion. 3.2% of blood donors in Brazil were found to carry Bartonella in their blood. Bartonella DNA has been found in dust mites. Those with arthropod exposure have an increased risk, as well as those working and living with pets that have arthropod exposure. 28% of veterinarians tested positively for Bartonella compared with 0% of controls. About half of all cats may be infected with Bartonella – as high as 80% in feral cats and near 40% of domestic cats. In various studies dogs have close to a 50% rate as well. Evidence now suggests it may be transmitted congenitally from mother to child – potentially leading to birth defects.
I’m glad they mentioned:
infections of their spleen & liver
involvement of the eye
Because, these are the things crossing my desk on a daily basis.
Bartonella is prolific, tenacious, and can cause severe illness, and many LLMD’s consider it a major coinfection of Lyme.
https://www.ncbi.nlm.nih.gov/pubmed/19303175 Besides the case report of a woman with osteomyelitis, the study states a literature review identified 51 other cases of osteomyelitis associated with cat scratch disease, 14 of those confirmed by PCR.
Bartonellosis is a term used to encompass all infections caused by pathogenic Bartonella species. Bartonella are emerging, flea-borne bacteria that are highly adapted to living in mammalian hosts and are implicated in a wide spectrum of diseases in humans and animals.
As a genus, these bacteria cycle from the blood to tissues around the body making them difficult to detect and identify. There were only 2 named Bartonella species prior 1990, but now there are about 20 species associated with human disease.Bartonella henselae, the causative agent of Cat Scratch Disease (CSD), is the most common species found in both animals and humans in the United States. Although the first case was described in the 1950s, B. henselae was not identified until extensive research on HIV patients was performed in the 1990s.
Bartonellosis was originally thought to primarily affect immunocompromised individuals because a normal immune system could self-regulate the infection. However, recent research has suggested that immunocompetent people can be chronically infected, but be asymptomatic or show atypical symptoms. Furthermore, these chronic infections can lead to cardiac and neurologic complications that are life threatening. Read on to learn more about symptoms, risk factors, and the testing options that Galaxy Diagnostics offers for Bartonella.
Acute vs. Chronic Bartonellosis
Research on Bartonella species has increasingly suggested its role in chronic diseases ranging from neurovascular to rheumatologic.
Despite these findings, reported cases are often focused on acute infections, such as CSD, Trench Fever, and Carrion’s disease, that show typical clinical signs making them easier to diagnose. Acute infections are likely to be diagnosed and treated quickly, but the story is different for chronically ill patients that are atypical or asymptomatic.
Chronically ill patients may show non-specific symptoms, like headaches, malaise, or fatigue, in the beginning of the infection. As the Bartonella species causes inflammation in different tissues around the body, symptoms can resolve and relapse in a cyclic pattern. Furthermore, co-infections have been been documented with other bacteria (Borrelia burgdorferi, Anaplasma, etc.) and parasites (Babesia microti, Theileria) which complicates clinical diagnosis of chronic bartonellosis even more. Unfortunately, these chronic infections are often mistaken for other disorders, such as immune-mediated diseases (lupus, multiple sclerosis, etc.), and lead to additional economic and health concerns. Patients who were diagnosed after unknowingly struggling with bartonellosis shared their stories to help shed light on the complexity of these diseases.
So what does Bartonellosis look like?
That can be a hard question to answer for researchers, physicians, and specialists alike. Bartonellosis can present in many ways, and atypical manifestations make it even harder to accurately describe clinical patterns. Nevertheless, Bartonella infection is successfully diagnosed in patients all over the world, and awareness of the classic presentation of the disease can help guide diagnosis. There are classic signs that make some cases easier to diagnose than others.
Cat Scratch Disease (Bartonella henselae)
Cat Scratch Disease (CSD) is the most common Bartonella infection diagnosed in humans and animals across the United States. Bartonella henselae, the causative agent, is a flea-borne bacterium that is transmitted between mammal reservoirs through arthropod vectors, like biting flies and ticks. The primary reservoir animal for this species is a cat, but has also been found in horses, dogs and wild animals, such as bats. CSD is typically diagnosed after a scratch from a cat, hence the name, but in some cases patients cannot recall a recent scratch or bite.
Trench Fever (Bartonella quintana)
Trench fever is a common manifestation of bartonellosis that is primarily transmitted by human body lice (Pediculus humanus humanus). It is best known for causing fever, headache, and leg pain in over one million soldiers in Europe during World War I. These soldiers were subjected to poor hygiene and lack of cleanliness that created a breeding ground for arthropod vectors such as body lice. Although trench fever has been around for a long time, the causative agent, Bartonella quintana, was only isolated in 1960 by J.W. Vinson. Currently, B. quintana infection is a higher risk for people who are homeless and more likely to be exposed to infected lice. Mammalian transmission of this pathogen is also possible and was documented in 2007 when a North Carolina woman tested positive after being bitten by a feral cat.
Carrion’s Disease (Bartonella bacilliformis)
Carrion’s disease is named after a Peruvian medical student named Daniel Carrion. Carrion inoculated himself with fluid from verruga peruana lesions in order to document the symptoms that followed, but he died five weeks later. In 1909, a researcher named Alberto Barton was the first to publish Bartonella bacilliformis as the causative agent of Carrion’s disease. It is transmitted by infected sand flies (Lutzomia verrucarum) that bite human hosts primarily in Peru, Ecuador, and Columbia. Despite being geographically isolated, cases have also been described in travelers to South America months to years after returning to non-endemic countries. This infection often presents itself as an acute illness, referred to as Oroya fever, as well as a chronic condition called verruga peruana (Peruvian warts).
Endocarditis is inflammation of the inner lining and valves of the heart, typically caused by the presence of bacteria or a viral pathogen. Endocarditis typically presents with non-specific clinical signs such as chills, fatigue, or muscle pain, but can have devastating long-term effects that may require surgery to replace the valves. Death may result if endocarditis is not diagnosed and treated early enough. When imaging shows the disease, physicians will collect samples to culture so a causative pathogen can be identified.
Culture-negative endocarditis, in which a pathogen cannot be readily isolated, represents up to 31% of all human cases. When this is the case, Bartonella species are often the culprit. Since 1993, a wide spectrum of Bartonella species have increasingly been implicated in endocarditis in humans and dogs. Nine Bartonella species in humans and seven Bartonella species in dogs have been identified as the pathogenic bacteria for endocarditis. Researchers are currently working on ways to improve diagnosis of Bartonella in these cases, but the nature of this stealth pathogen makes it difficult. When physicians are faced with patients suffering from endocarditis, risk factors for Bartonella species should be taken into account.
The prevalence and incidence of Bartonella species can vary depending on geographic location. For example, you are more likely to contract B. quintana in South America, but B. henselae is commonly found in North America. Furthermore, certain regions of North America, such as the southeastern United States, have more reported cases of Cat Scratch Disease than anywhere else in the United States. On top of this, seasonality and climate seem to affect the exposure rates of Bartonella species. Cases of bartonellosis have been reported around the world, however, so testing should be considered when the risk is high. There are common risk factors that contribute to contracting any type of bartonellosis:
Outdoor or indoor exposure to fleas, biting flies, ticks, and other arthropods
People with naturally weaker immune systems (younger children, adolescents, aging adults)
Cancer patients, people with immune disorders (lupus), or patients using immunosuppressants for therapeutic reasons (such as steroid therapy)
Successful diagnosis of bartonellosis can be difficult due to the variety of atypical and non-specific symptoms that an infected person may have combined with the stealthy nature of the pathogens. Bartonella tends to be present at low levels and does not invoke a strong immune response. As Bartonella species cycle from blood to tissues, symptoms change along with the host’s immune response. Despite vast advances in diagnostic tools over the last century, conventional methods lack sensitivity. Multiple rounds of testing may be required before a positive result is achieved. Researchers are looking for new ways to detect Bartonellapathogens to save patients time, money, and frustration. Current methods include:
Culturing methods are used to grow bacteria on a specifically formulated medium from samples such as blood and tissues from around the body. These methods have continued to evolve as knowledge of Bartonella species improves. Most recently, the use of liquid growth medium based on insect cell growth requirements has shown increased growth for multiple species. Successfully matching the strict growth requirements for Bartonella species makes it more likely to isolate and detect them. Patented BAPGM (Bartonella Alphaproteobacteria growth medium) is used in combination with PCR at Galaxy Diagnostics to maximize sensitivity.
Serology refers to the use of the host immune response to detect the presence of Bartonella. When Bartonella is present, the immune system creates IgG and IgM antibodies to fight it. Methods such as immunofluorescence assays (IFA), enzyme immunoassays (EI), and enzyme-linked immunoassays (ELISA) use these antibodies to infer infection from Bartonellaspecies. However, there are various limitations to serology. First, Bartonella species are able to evade the immune response because they are present in small amounts and engage in evasive strategies such as residing inside of red blood cells. Even if antibodies are present, it does not mean that Bartonella bacteria are actively present. There are also concerns with cross-reactivity between other bacteria that may lead to false positives. However, this method of detection is useful for monitoring treatment response because it is typically cheaper than other methods and provides a record of antibody amounts for a given period of time.
PCR (polymerase chain reaction) is a method of detecting bacterial DNA in the blood and tissues of patients. By designing primers (small pieces of DNA) that match Bartonella DNA sequences at the genus or species level, it is possible to use an enzymatic reaction to amplify bacterial DNA that is present. This method confirms active infection, but this platform has difficulties as well. As mentioned earlier, Bartonella tend to infect at low levels. PCR has a chance of missing DNA if only a small amount is present. Furthermore, PCR can result in false positives if the wrong sequence of DNA is amplified. Positive results from PCR should always be verified by sequencing to ensure that it is Bartonella and not another bacteria. Galaxy Diagnostics’ ePCR method combines a patented culture formulation with PCR and sequencing to maximize sensitivity and specificity.
Bartonellosis is treated with antibiotic therapy, but the type(s) of antibiotics selected and the duration of treatment vary with the nature of the infection and must be evaluated by a physician on a case-by-case basis. Typically, acute infections can be treated with 10-21 days of antibiotic therapy. However, treatment failure can occur. Relapse of symptoms has been documented in numerous cases and chronic infections can take longer to treat.
Norway rats (Rattus norvegicus) and black rats (R. rattus) are known to be cosmopolitan reservoirs for zoonotic agents. Nevertheless only little is known about prevalence and distribution of arthropod-borne pathogens in rats from Europe. Therefore this survey was focused on the detection of arthropod-borne pathogens. Spleen-derived DNA samples were available from 528 Norway rats and from 74 black rats collected in several European countries. Further, these samples were processed by PCR for the detection of zoonotic pathogens such as Anaplasma phagocytophilum, Candidatus Neoehrlichia mikurensis (CNM), Babesia spp. and Bartonella spp. eventually followed by sequencing.
Babesia spp. was not detected. Four Norway rat samples were positive for A. phagocytophilum DNA and two for CNM. In 50 rat samples Bartonella spp. DNA was detected (8.1%; 95% CI: 6.2-10.61). Whereas B. tribocorum (n=45) and B. grahamii (n=1) were exclusively carried in Norway rats from Central Europe (Belgium, Germany), B. coopersplainsensis (n=4) was only detected in black rats from southern European countries (Spain, Italy).
Pathogenic Bartonella spp. DNA was found in black and Norway rats from Germany, Italy, Spain and Belgium for the first time. Bartonellae were found focally in zoos suggesting Norway rats as possible reservoir for B. tribocorum and black rats for B. coopersplainsensis in Europe. These findings should raise awareness of pathogenic Bartonella spp. in Norway rats especially in terms of pest management control in zoos. Norway and black rats seem not to be predominantly involved in the life cycle of the other examined arthropod-borne pathogens in Europe.
A Brief History of Three Diseases Caused by Bartonella
The oldest indication of human Bartonella infection (bartonellosis) was found in a tooth of a person who died about 4,000 years ago.
The history of the scientific description of Bartonella is much shorter. Three acute diseases caused by these bacteria—trench fever, Carrión’s disease, and cat scratch disease—were only scientifically described starting toward the end of the 19th century, and chronic infection was only recognized at the end of the 20th century. At the start of the 21st century, accurate tests and effective treatments are the main challenges that Bartonella researchers are focused on.
Trench fever, also called five-day fever, is most commonly seen today in underhoused and homeless populations. It was first identified in soldiers involved in the trench warfare of World War I, where the unhygienic and crowded conditions allowed vectors like body lice to thrive. These soldiers called it “shin bone fever” because of the associated leg pain. Up to a third of British soldiers and up to a fifth of German soldiers are believed to have been infected. Famous veterans, including the writers J.R.R. Tolkien and C.S. Lewis, are among those who developed the disease.
During World War I, Major W. Byam and members of the British military proved that body lice transmitted the disease. Their results were published in 1919. They found that they could diagnose Bartonella quintana by allowing uninfected lice to feed on the patient and then inspecting the lice for signs of bacteria.
Bartonella quintana (“quin” is the five in five-day fever) was proven to be the causative agent of trench fever in in the 1960s by J.W. Vinson. Vinson, working for the United States Army, was able to culture the bacteria in blood. Vinson proved the bacteria caused trench fever by infecting body lice and allowing the lice to bite volunteers.
As Europe was hurtling toward World War I, immigrant laborers on the other side of the world were facing another species of Bartonella. The disease caused by Bartonella bacilliformis sometimes showed up as fever and severe anemia and sometimes involved characteristic wart-like skin nodules. The nodules, referred to now as Peruvian warts, appear on a carved human figure that is more than 2,000 years old.
By the time the immigrant laborers were falling ill, the illness had come to be called Carrión’s disease. Daniel Alcides Carrión Garcia had proven in 1885 that the skin nodules were related to the fever illness by infecting himself from a skin nodule. He subsequently died from the infection. The Peruvian government declared him a national hero in 1991.
The workers on the La Oroyo-Lima railway in Peru were sickening and dying at a rate previously unseen. By the time the outbreak was over, as many as 10,000 had died. In 1905, Dr. Alberto Leonardo Barton Thompson found a bacteria in their blood that we now call Bartonella bacilliformis. For this discovery he received the Orden del Sol de la Nación from Peru and when the genus Bartonella was separated from Rickettsia it was named for him.
Apart from war and hard labor, cat scratch disease was a condition that struck in the home. Children often experienced the symptoms of fever and inflamed lymph nodes. Though humans had likely experienced cat scratch disease for thousands of years, the symptoms were first described scientifically in 1889 by Henri Parinaud, a French physician.
In 1950, Robert Debre further specified the syndrome and identified cats as the reservoir for the bacteria. After a misstep in which Afipia felis was thought to be the causative bacteria, further study of the antibody reactions of patients with cat scratch disease clarified that Bartonella henselae and another species, Bartonella clarridgeiae, were responsible for cat scratch disease.
In 1985, a clinical microbiology technologist at the University of Oklahoma collected samples during an outbreak. Her name is Diane Marie Hensel and the bacteria she collected, Bartonella henselae, was named for her.
By the 1990s, the emergence of Bartonella henselae infections in patients with HIV was making clear that more people were infected with the bacteria than just those exhibiting the symptoms of cat scratch disease. In the past, it was thought that cat scratch disease was self-limiting and that only immunocompromised people (people with reduced immune systems) would develop symptoms. However, Bartonella species have increasingly been implicated in chronic diseases with non-specific or atypical symptoms.
Galaxy Diagnostics co-founders Ed B. Breitschwerdt and Ricardo G. Maggi, along with Galaxy Diagnostics medical director Dr. Robert Mozayeni, have published key research expanding the understanding of acute and chronic bartonellosis. In 2014, Dr. Paul M. Lantos of Duke University, Drs. Breitschwerdt and Maggi, and others published the results of a study documenting Bartonella infection as an occupational risk of veterinarians. Ongoing research is being conducted to learn more about the prevalence of Bartonella infections in people without obvious signs of the named conditions caused by Bartonella, but it is at an early stage.
This history covers only three common species of Bartonella. At this time, two dozen species have been identified and more are suspected to exist. The symptoms that these new species may cause and how they are transmitted are not clear, but scientific methods have thankfully improved immensely since the end of the 19th century. Galaxy’s patented ePCR process is being used in research right now to further the understanding of Bartonella species and their associated diseases around the world.
Byam, W. et al. (1918). Trench fever: A louse-borne disease. Transactions of the Royal Society of Tropical Medicine and Hygiene, 11(7), 237-284.
Cat-scratch disease (CSD) is usually a self-limiting infection that in the majority of cases occurs as lymphadenitis in children who have been scratched or bitten by a cat. Rarely, Bartonella henselae is cause of fever of unknown origin (FUO), with dissemination to various organs, mimicking an inflammatory rather than a lymphoproliferative disease. This manuscript will present a case of thoracic manifestations of CSD in an immunocompetent 2-years baby without history of cat contact, with fever of unknown origin, investigated by chest CT and MRI.
The myths surrounding Bartonella are getting shattered one by one. More and more cases are showing immunocompetent people contracting Bartas well as folks who have had no exposure to cats. Time for NEW Research and open minds! Bartonella, like so many other pathogens needs an entirely new approach. Nothing about this should be reported as “rare.” Nobody has a clue on prevalence!