About Vector-borne Diseases
Traditionally in medicine, a vector is an organism that does not cause disease itself, but which spreads infection by conveying pathogens from one host to another. This sense of “biological vector” is the primary one in epidemiology and in common speech. Lyme borreliosis or Lyme disease is one of the most common among vector-borne diseases and the carriers are often ticks. However, as a tick can transmit up to 100 different infections, it shares common traits with other hosts transmitting some of the same infections – hence the name “vector-borne”. Examples of other vectors are lice, fleas, mice, mosquitos etc. They carry bacteria, viruses, multicellular microscopical parasites and other pathogens that may transmit a disease through feeding activity. In the following, a general outline on tick-borne diseases such as Lyme Borreliosis and other associated infections will be presented.
Lyme Borreliosis
Infections transmitted by ticks are well known. Lyme borreliosis is one of the most known illnesses to be transmitted by ticks. It is a multi-system infectious disease caused by a bacterial spirochete, Borrelia burgdorferi (hereafter Bb). The name Lyme disease originated in 1975 when the town Old Lyme in Connecticut experienced an outbreak of rheumatoid arthritis, which one eventually (1978) discovered was caused by ticks. The cause of Lyme disease remained unknown until 1982 when an American scientist, Dr. Willy Burgdorfer, identified a Borrelia- spirochete to be the cause, hence the name Borrelia burgdorferi. Although the illness received it’s name a few decades back, recent discoveries found that the 5300 year old Ötzi indeed had been infected with Bb.
Bb is the most common species in the United States; there are 100 strains in the US alone and 300 strains worldwide. There are at least 15 species that are infectious to man, including B. garinii, B. afzelii, B. japonica, B miyamoto, B lonestari, and B andersonii. Bb is the most genetically complex bacteria identified to date. Bb contains 132 functional genes, compared to the syphilis spirochete Treponema pallidum (often called the Bb’s “cousin”) with mere twenty-two. Ninety percent of these genes are novel to all bacteria. Bb’s genome is 2/3 the size of the human genome. Bb contains 21 plasmids, more than any other bacteria. This characteristic allows the organism to be highly adaptive to its environment, with the ability to survive in a number of different hosts.
Bb appears to survive even when the host has an intact immune system. Bb is not commonly found in body fluids, but rather has an affinity for collagenous tissue, such as the bladder wall, synovium, myelin sheath of nerve fibers, and the meninges. The bacteria can, in the early stage of the disease, disseminate to distant areas, it can hide in niches, it can be intracellular, and it can express multi-drug resistance. Further, it can hide in biofilms both in the blood and in anoxic, remote parts of the body, and camouflage itself with proteins from the host. It may perform antigenic changes, manipulate the immune system of the host, and change into inactive (dormant) cyst-forms. All these properties make specific Borrelia spirochetes unique, and some could potentially develop disease of epidemic proportions. Bb is called “The Great Imitator”, and seems to be the cause of a tremendous amount of misdiagnoses worldwide.
Lyme Borreliosis offers a complex symptom picture for the clinician. Infection with Bb may be overlooked due to common misperceptions about disease presentation and pervasiveness. Lyme Borreliosis can be misdiagnosed as Fibromyalgia, ME/CFS, Multiple Sclerosis, Lupus, Parkinson’s, Alzheimer’s, Rheumatoid Arthritis, ALS, and a number of neuropsychiatric disorders. Lyme Borreliosis has often been referred to having three stages. Stage 1 (3-30 days post-tick bite) is called early localized Lyme Borreliosis, as the infection has not yet spread throughout the body. Symptoms include, but are not limited to a red, expanding rash called erythema migrans (EM), fatigue, chills, fever, headache, muscle and joint aches, and swollen lymph nodes. Studies have shown that only half of the infected patients develop an EM. Also, several patients do not even recall ever having a rash. Stage 2 is called early disseminated Lyme Borreliosis (days to weeks post-tick bite). Untreated, the infection may spread from the site of the bite to other parts of the body, producing an array of specific symptoms that may come and go, including; addditional EM lesions in other areas of the body; facial or Bell’s palsy (loss of muscle tone on one or both sides of the face); severe headaches and neck stiffness due to meningitis (inflammation of the spinal cord); pain and swelling in the large joints (such as knees); shooting pains that may interfere with sleep; heart palpitations and dizziness due to changes in heartbeat. Stage 3 is called late disseminated Lyme borreliosis, where the bacteria have spread throughout the body (months-to-years post-tick bite). Approximately 60% of patients with untreated infection may begin to have intermittent bouts of arthritis, with severe joint pain and swelling. Large joints are most often affected, particularly the knees. Untreated or undertreated patients may also develop chronic neurological complaints months to years after infection. These include shooting pains, numbness or tingling in the hands or feet, and problems with short-term memory.
Today, there are few, if any, highly sensitive and reliable tests for detecting Bb, and there is an assumption of a high number of zero negative (“false negative”) patients suffering from this infection. Studies have shown an average of 56% sensitivity to Bb with a two-tiered testing (Elisa and Western Blot). This would be the same as flipping a coin. Some studies show as low as 29% sensitivity. According to a recent report from CDC (Centers for Disease Control and Prevention), the annual number of humans infected with Lyme Borreliosis is 10 times higher than previously estimated – 300.000 Americans per year. It becomes clear that this is a worldwide epidemic, with official numbers revealing an annual frequency that is six times higher than HIV/AIDS.
There is a discrepancy in the medical community regarding which approach to take regarding diagnostics and treatment. This originates from the US where the two organizations IDSA and ILADS have two very differing views. IDSA (The Infectious Diseases Society of America) stipulates that it is an easy disease to diagnose and treat. The diagnostics rely mainly on a two-tiered testing regime (of Elisa and Western Blot). Treatment should not exceed 14- 28 days with antibiotics. After this maximum treatment of one month, IDSA states that the infection is treated, and what the patient experiences beyond this point, is a Post-Treatment Lyme Disease Syndrome (PTLDS), not related to an active infection. ILADS (International Lyme and Associated Diseases Society) was founded by medical doctors (1999), who realized that the official treatment guidelines were not making the patients better. ILADS also puts a stronger emphasis on the clinical presentation, as the current diagnostics still are too uncertain. ILADS claims that an untreated infection of Bb may go chronic. Longer treatment regimens and a combination of several types of antibiotics is important to get well. ILADS arranges several times a year knowledge leading conferences to bring together respected international researchers and clinicians to share cutting-edge research and diagnostic and treatment modalities that will enhance the lives of those suffering from these diseases. Increasingly more doctors now treat according to the ILADS guidelines. A total of 56% of American doctors follow the ILADS guidelines, and increasingly more states have passed doctor protection laws that let their physicians treat according to the ILADS guidelines. A recent example is the Vermont legislature that just passed Lyme bill H123, which acknowledges the severity of chronic Lyme disease, the role of co-infections in chronic illness, and the need for individualized treatment according to ILADS guidelines. The bill also contains language that protects health care practitioners from disciplinary action from the Vermont board of medical practice for diagnosing and treating tick-borne diseases according to ILADS guidelines, allowing practitioners to treat according to their best clinical judgement. This is a huge political step forward, and Vermont now joins a growing number of other states that have passed doctor protection laws.
This fundamental dispute has played out, not only in the universities, research communities or in the doctor’s office, it has also been taken to court as well as to the Senate and the Congress. Attorney General, Blumenthal waded into the Lyme disease controversy in 2006 when he launched an antitrust investigation into guidelines for treating Lyme developed by IDSA. The guidelines, which advised against long-term antibiotic therapy, had been used by insurers to restrict coverage for long-term treatment. Blumenthal alleged that some members of the panel that developed the guidelines had conflicts of interest, including financial stakes in drug companies or diagnostic tests. In April 2008, IDSA entered into an agreement with Connecticut Attorney General Richard Blumenthal to voluntarily undertake a special review of its 2006 Lyme disease guidelines. The outcome of the investigation was that 9 out of 14 of the IDSA authors had some kind of commercial stake (insurance, lyme vaccine etc.), however the guidelines were not revised. A study from 2011, also showed that 50% of random IDSA guidelines from 1994-2010 were based on low scientific quality and the authors warned that physicians should remain cautious when using current guidelines as the sole source guiding patient care decisions. Despite this fundamental disagreement, there is still a common understanding, that we still have a long way ahead when it comes to filling in the unknowns in biology and epidemiology of this disease. Whilst waiting for more research to be conducted, there are unfortunately a significant number of patients that suffer tremendously.
Lyme Borreliosis may be transmitted together with other vector-borne infections. The most common co-infectious organisms are Bartonella spp (Bartonellosis), Babesia microti (Babesiosis), Ehrlichia spp & Anaplasma phagocytophila (Ehrlichiosis). A growing number of studies report the importance of identifying co-infections as additional infections next to Lyme Borreliosis. DeMartino, Carlyon et al. found that every fifth individual who was seropositive for Bb also showed immunological evidence of exposure to Ehrlichiosis (2001). Prevalance of Babesiosis can range from 10% to 60% in individuals who are seropositive for Bb. In a random selection of Ixodes scapularis ticks in New Jersey, 33.6% were positive for Borrelia burgdorferi, 8.4% for Babesia, 1.9% Anaplasma, and 34.5% Bartonella. Please see an outline of different co-infections outlined below.
Bartonellosis
Bartonellosis, a globally emerging vector-borne zoonotic bacterial disease, is caused by hemotropic, gram-negative, aerobic, facultative intracellular Bartonella spp and has a 22-24 hour division time. Of the 30 Bartonella species/subspecies, 17 have so far been associated with human infections. According to Dr. Breitschwerdt (2012), Bartonella is transferred via fleas more often than ticks BUT that most of the ticks he is testing show positive for one or more strains of Bartonella. Vets should in particular be careful, as well as people that are around farm animals, pets and arthropods (fleas, ticks as lice) are in risk groups. Cats are one of the most likely and common reservoir. This family of bartonella bacteria resides inside the red blood cells, in the endothelial cells, microglial cells, macrophages, CD34 stem cells, and bone marrow stem cells. Bartonella is seen as a stealth pathogen. It can suppress the host’s immune system – so that it is not detected as an intruder, and hence the immune system will not fight it. It can give chronic, long-term infections, and is not easy to treat, although there are medical communities claiming it will pass even without treatment. The severity of the infection will vary among individuals and may present overlapping symptoms with borreliosis and babesiosis and is difficult to diagnose. PCR tests are often used, however, due to low sensitivity, the tests often come back negative. Some common symptoms of Bartonella are severe insomnia, migraines, anxiety, panic-attacks, brain fog, and aggression, but not everyone has these. It can also cause endocarditis, chronic fatigue, tenderness in muscles, chronic pain, vomiting, fever/chills, neuropathy in any part of your body, ringing in the ears, joint pain, skin rash, and stretch marks. Burrascano (2008) suspects bartonellosis when neurologic symptoms are out of proportion to the other systemic symptoms of chronic Lyme. He also notes gastritis, lower abdominal pain, sore soles, and tender subcutaneous nodules along the extremities. Lymph nodes may be enlarged and the throat can be sore. As bartonellosis and babesiosis both might cause a suppression of the immune system, it is now acknowledged as essential that co-infections are detected and treated simultaneously to borreliosis for a better treatment outcome. Various Bartonella spp. have been identified in domestic and wild animals, including canids, deer, cattle, rodents, and marine mammals.
Anaplasmosis/ Ehrlichiosis
Anaplasma phagocytophilum is one of the most widespread transmitted tick-borne pathogen affecting livestock in Norway – causing vast losses of sheep. It can also lead to disease in humans. The micro-organism infects lymphocytes – and will lead to a suppression of the immune system (as with Bartonella, Babesia and Borrelia). It seems to be a common co-infection associated with Lyme disease, which then potentially creates a far more complex clinical presentation. It is diagnosed through serology, PCR and microscopy. The clinical manifestations of ehrlichiosis and anaplasmosis are the same. Each is often characterized by sudden high fever, fatigue, muscle aches, headache. The disease can be mild or life-threatening. Severely ill patients can have low white blood cell count, low platelet count, anemia, elevated liver enzymes, kidney failure and respiratory insufficiency. Older people or people with immune suppression are more likely to require hospitalization. Deaths have occurred.
Mycoplasmosis
Mycoplasma is not considered tick-borne, but is often found as a co-infection in patients battling with tick-borne diseases. Mycoplasma are pleomorphic bacteria which lack a cell wall and as a result, many antibiotics are not effective against this type of bacteria. There are over 100 known species of Mycoplasma, but only a half dozen or so are known to be pathogenic in humans. The pathogenic species are intracellular and must enter cells to survive. Once they are inside the cells, they are not recognized by the immune system and it is difficult to mount an effective response. The most common type is Mycoplasma pneumonia, presenting upper and lower respiratory infections. For children 3-15 years of age, this is the most common cause of pneumonia. According to The National Institute of Health in Norway (FHI) humans are the only reservoir for Mycoplasma pneumonia. Lyme Borreliosis patients that have Mycoplasma infections may present symptoms like; fever, chills, generalized weakness, gastrointestinal symptoms (anorexia, nausea, abdominal pain, vomiting, diarrhea, among others), anemia, muscle and joint pain, respiratory problems and dark urine. The combination of Borrelia, Mycoplasma and Babesia infections can be lethal in some patients (about 7% of patients can have disseminated intravascular coagulation, acute respiratory distress syndrome and heart failure), but the majority of patients with tend to have the chronic form of the disease. Mycoplasma pneumonia is likely to occur in about 10% of mycoplasma infections. The signs and symptoms of Mycoplasma infection are highly variable and thus it is not uncommon for a diagnosis to be entirely missed. A partial list of symptoms includes chronic fatigue, joint pain, intermittent fevers, headaches, coughing, nausea, gastrointestinal problems, diarrhea, visual disturbances, memory loss, sleep disturbances, skin rashes, joint stiffness, depression, irritability, congestion, night sweats, loss of concentration, muscle spasms, nervousness, anxiety, chest pain, breathing irregularities, balance problems, light sensitivity, hair loss, problems with urination, congestive heart failure, blood pressure abnormalities, lymph node pain, chemical sensitivities, persistent coughing. A study by Nicholson (2008), as many as 75% of Lyme Borreliosis patients appear to have Mycoplasma infections, and yet Mycoplasma is often overlooked in the diagnosis and treatment of chronic Lyme disease, neurodegenerative diseases, and many other chronic illnesses lacking clear origins.
Babesiosis
Babesia is a blood parasite (a protozoan, so called one-celled parasite) that invades and lives within red blood cells. It is an intracellular infection. The parasite can be transmitted via ticks, migrants, mice and cattle. There are over 100 species of this parasite, and about 20 that may cause illness in humans. It is hard to detect due to low parasitemi. The most acknowledged way of diagnosing babesiosis is through microscopy – adding giemsa (a dye that makes it easier to see the parasite as it is free from pigments and chizontes, much like malaria). Should the “malteser-cross” reveal itself under the microscope, you have a solid evidence that Babesia is present in the blood. Even though microscopy is the “golden standard” for diagnosing Babesia, hospitals often use PCR instead. As the parasitemi is cyclic, it seems that regular PCR easily can present false negatives, and it is recommended to perform repetitive tests.
As we have discovered at least 20 Babesia types/species that may cause infections in humans, this can explain why the clinical picture of this illness will vary. A slowly progressing infection with babesia will present itself in a complete different and more asymptomatic way, as the parasite is known to have an extremely long incubation time in the human body. It seems that rodents do not get sick from these micro-organisms; however, they live happy as perfect sources of transmission. Many types of mice live on meadows and marshes eating grass. They stay in places where ticks are most certainly present.
There is documentation claiming that humans indeed can live well with Babesia in the blood – and not get sick. However, it can also give an on-going infection presenting many non-specific symptoms. It seems to be one of the most common co-infections with Bb. Also, as the symptoms of Bb and co-infections (e.g. babesiosis) overlap, and diagnostics are weak, there is reason to believe that many Borrelia-infected patients also suffer from babesiosis without having been diagnosed. As this is a parasite, and not bacteria, the treatment will not be the same as with Lyme disease. Hence, in cases of insufficient results with antibiotic treatment for Lyme Borreliosis, one may start to suspect the presence of babesiosis as a co-infection. Symptoms may include: Fever (often in initial stage of the infection), chills, shortness of breath, difficulty with temperature regulation, night sweats, stiffness in neck and other muscle groups, dizziness, flu like symptoms, malaise, fatigue, stomach pain, headache, intracranial pressure etc. Babesiosis is usually treated with malaria-medicines, however in the most severe cases, blood transfusion may be required.
In a new study from January 2015, published in the Journal of Clinical Microbiology and Infection, 199 anonymous patients from Belgium with known tick bite and symptoms of vector-borne disease were tested for Babesia using Indirect Fluorescent Antibody Test. The serological screen detected positive reactivity in 9% (n = 18) against B. microti, 33.2% (n = 66) against B. divergens, and 39.7% (n = 79) Babesia sp. EU1, respectively. This come to show that Babesia might be more widespread in humans that previously anticipated.
Tick-borne Encephalitis (TBE)
Tick-borne encephalitis, or TBE, is a human viral infectious disease that involves the central nervous system. The disease is most often manifested as meningitis (inflammation of the membrane that surrounds the brain and spinal cord), encephalitis (inflammation of the brain), or meningoencephalitis (inflammation of both the brain and meninges). It is most commonly known as a neurologic disease, however mild febrile illnesses can also occur.TBE is caused by tick-borne encephalitis virus, a member of the family Flaviviridae, and was initially isolated in 1937. There are three sub-types : European or Western tick-borne encephalitis virus, Siberian tick-borne encephalitis virus, and Far eastern Tick-borne encephalitis virus (formerly known as Russian Spring Summer encephalitis virus).There is no specific drug therapy for TBE. It requires hospitalization and supportive care based on syndrome severity. Anti-inflammatory drugs, such as corticosteroids, may be considered under specific circumstances for symptomatic relief.
There are also other co-infections that might be present in a patient with Lyme Borreliosis. Not all are vector-borne. Some of these might be chronic infections that get reactivated when having Lyme Borreliosis (E.g. EBV). In the following a few examples of other disease causing pathogens are listed. Filaria, Amebias, Giardia, TBE, Epstein Barr Virus, HHV-6, HHV-8, Cytomegalovirus, West Nile virus, Powassan encephalitis, Various viral encephalitis, RMSF, Typhus, Tularemia, Q-Fever, Brucellosis, Tick Paralysis, STARI, B. miyamotoi etc.
Today, there are an increasing number of patients suffering from vector-borne diseases. The patients being diagnosed and treated early in the course do not pose great challenges. The challenges become evident with patients where the illness has progressed and become chronic.
A more modern picture of a patient struggling long-term with vector-borne diseases, outlines a person with multiple infections that have turned chronic. The infections present themselves almost as a syndrome, where bacterial, parasitic and viral infections, together with an immune system out of balance, high levels of inflammation, insensitivity to environmental toxins and lowered ability to detox make these diseases hard to diagnose and treat. When adding sleep disorders, hormonal dysregulations etc, the patients are not easy to treat –and often end up seeking doctors after doctors for help. In order to achieve full recovery, it is vital that all issues are detected and addressed correctly in order to achieve recovery. Hence, as vector-borne diseases still demonstrate a big puzzle– it is essential that medical communities continue to research all aspects of this area. Improved diagnostics and courses of treatment are needed. A patient with vector-borne diseases needs to get individual diagnostic and treatment, just as many countries now are individualizing treatment for cancer patients.
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*Under continuous review. Last updated February 2nd 2015