This is why the higher dose is recommended if the disease is affecting the central nervous system, and IV ceftriaxone is not thought appropriate.
The minimum length of treatment recommended by NICE is 21 days and patients should complete the entire course even if they feel they have recovered earlier.
In some cases recovery may happen very slowly in the months following treatment. If patients get worse after treatment has finished, they should consult their doctor in case re-treatment is necessary, as NICE Guideline suggests. Although a House of Lords debate supported a call for development of a national network of interested NHS clinicians, the NHS has as yet no specialists in Lyme disease.
Because young children are usually smaller, those aged 12 and under are prescribed antibiotic dose according to their body weight, rather than the standard adult dose. Children aged under 9 are not recommended to have doxycycline because of side effects, and so amoxicillin is used instead. However, because amoxicillin does not penetrate the spinal fluid so well, IV ceftriaxone is recommended by NICE when the disease is affecting the central nervous system Lyme neuroborreliosis or the heart Lyme carditis.
Doctors and parents should be aware that in children, a neurological examination may be normal despite infection reaching the central nervous system. Patients might experience a worsening of symptoms on starting treatment. The reaction can start between 1 and 12 hours after antibiotics are started but can also occur later and can last for a few hours or 1 or 2 days.
The reaction is self-limiting and usually resolves within 24 to 48 hours. In Britain, medical education is highly variable regarding diseases transmitted by ticks.
This is called a Herxheimer reaction and occurs when the antibiotics start to kill the bacteria. In the first 24 to 48 hours, dead bacterial products stimulate the immune system to release inflammatory cytokines and chemokines that can cause increased fever and achiness. This should be transient and last no more than a day or two after the initiation of antibiotics. The most common side effect of the penicillin antibiotics is diarrhea, and occasionally even serious cases caused by the bacteria Clostridium difficile.
This bacterial overgrowth condition occurs because antibiotics kill the good bacteria in our gut. It can be helpful to use probiotics to restore the good bacteria and microbiome balance.
The prognosis after early treatment of Lyme disease is generally very good. The prognosis worsens, however, when diagnosis and treatment are delayed. Most patients with early Lyme disease infection recover with antibiotics and return to their normal state of health.
However, some patients suffer from ongoing or recurrent symptoms related to Lyme disease despite standard of care antibiotic therapy. Patients often call this condition chronic Lyme disease, although an agreed upon clinical case definition for chronic Lyme disease has proven difficult to reach a consensus on. This research definition is being used to investigate the potential causes of persistent symptoms in Lyme disease. Post Treatment Lyme Disease PTLD represents a research subset of patients who remain significantly ill 6 months or more following standard antibiotic therapy for Lyme disease.
PTLD is characterized by a constellation of symptoms that includes severe fatigue, musculoskeletal pain, sleep disturbance, depression, and cognitive problems such as difficulty with short-term memory, speed of thinking, or multi-tasking.
In the absence of a direct diagnostic biomarker blood test, PTLD has been difficult to define by physicians, and its existence has been controversial.
However, our clinical research shows that meticulous patient evaluation when used alongside appropriate diagnostic testing can reliably identify patients with a history of previously treated Lyme disease who display the typical symptom patterns of PTLD. Our research indicates the chronic symptom burden related to PTLD is significant.
Although often invisible to others, the negative impact on quality of life and daily functioning is substantial for PTLD sufferers. One study estimates that chronic Lyme disease and associated diseases could be the cause of over suicides per year in the USA [ 58 ]. However, oral antibiotics are much easier to administer, and they are not as expensive as IV antibiotics.
Hence, in a situation where a patient cannot afford IV antibiotics, or if a patient has difficulties finding someone to administer IV antibiotics, then oral antibiotics are always preferred over no antibiotics. Thus, similarities exist between chronic Lyme disease and the Human Immunodeficiency Virus HIV that also cannot be eradicated with oral medication.
Today people are becoming more aware of chronic Lyme disease. The conflict over what the best ways are to diagnose and treat Lyme disease have gone so far that a Tick-Borne Disease Working Group was created when the 21st-century cures act became law in the USA in December [ 66 ]. The objective of the working group is to review the scientific literature, regarding for example causes, prevention, diagnosis, duration, surveillance and treatment for Lyme disease and associated diseases.
In Herxheimer and Hartmann named such atrophy of the skin Acrodermatitis Chronica Atrophicans ACA [ 70 ] which is why ACA, which is dermatological disorder mostly associated with chronic Lyme disease in Europe [ 71 ], sometimes is called Herxheimer disease. ACA presents its self as a red-bluish discoloration of the extremities [ 72 ]. The link between Lyme disease and the bacteria that cause it was first discovered by the medical entomologist Dr.
Willy Burgdorfer in [ 73 ]. The bacteria, therefore, took the name after its discoverer Borrelia Burgdorferi. It was first in when the serendipitous discovery of penicillin was made by scientist Alexander Fleming [ 74 ] that treatment for Lyme disease became available. Penicillin was originally produced from mold. Naturally occurring antibiotics can also be produced by fermentation, an old technique that can be traced back almost years [ 75 ].
The genes that convey antibiotic resistance to bacteria have been around for at least 30, years [ 76 ], which means that antibiotic resistance to a large part has not been developed during the last 88 years humankind has known about antibiotics which is a fact that we rarely hear about though. One of the first people to treat chronic Lyme, or more specifically ACA, with penicillin in was Nils Thyresson [ 77 ] who was a Swedish medical doctor and professor of Dermatology and Venereology. Spirochete bacteria are believed to be much older this though.
Spirochetes similar to Borrelia has been found in a 15 million years old tick preserved in amber in the Dominican Republic [ 79 ] which means that the spirochete bacteria that causes Lyme disease is much older than humankind.
The complete Borrelia genome was first sequenced in [ 80 ]. The Borrelia bacteria has the most complex genomic architecture among known prokaryotes [ 81 ]. Borrelia bacteria are also very genetically diversified [ 82 , 83 ]. Different Borrelia strains have different antigens [ 84 ] which means that different Borrelia strains will produce different immune system responses in the form of antibodies in an infected host.
A blood test that only test for one specific antibody cannot detect antibodies from different Borrelia strains. A person that is infected with one type of Borrelia strain will also have different symptoms compared to a person that is infected with a different Borrelia strain [ 85 ].
For example, arthritis is usually not seen in European Lyme disease patients [ 86 ] due to the different Borrelia strains that exist in Europe compared to the USA which means that the lack of arthritis in a patient should not be interpreted as the patient not having Lyme disease. Lyme disease diagnosis and treatment are further complicated by the fact that Borrelia also has many different co-infections [ 87 ] such as Babesia, Bartonella, Ehrlichia, etc.
It is believed that a vector such as a tick can spread at least different types of bacteria [ 88 ] and many types of viruses [ 89 ] which means that many chronic Lyme patients might be infected with many different types of microbes at the same time. Money goes to the same people who have for the last thirty years produced the same thing. The Borrelia bacteria has at least three different morphological forms.
The Borrelia bacteria evade the immune system by for example changing morphology [ 94 ] and by changing its outer surface proteins Osp also known as antigens [ 95 , 96 , 97 , 98 ]. When the bacteria change its antigens all the time, the specific antibodies that are produced by the immune system to try to eradicate the infection becomes useless.
Immune system evasion by other diseases such as Amyotrophic Lateral Sclerosis ALS [ ] and cancer [ ] is also believed to be connected to G4. Exciting research is being done that is trying to find medications that block G4 for the Borrelia bacteria [ ]. If the researchers are successful, it could mean an end to chronic Lyme disease but also to other diseases. If the immune system in combination with some drug could eradicate the Borrelia bacteria that would be a superior solution compared to a possible lifetime of oral antibiotics.
The bacteria evade being killed by broad-spectrum antibiotics by changing morphology [ ]. Note that the bacteria ability to evade broad-spectrum antibiotics should not be interpreted as antibiotic resistant. Plaquenil raises the PH level in cells so that macrolide antibiotics can work more effectively [ ].
Unfortunately, Plaquenil does not work for tetracycline antibiotics [ ]. It is, however, important to note that Plaquenil can cause eye problems [ ] which means that not all patients can tolerate this medication. The recommended treatment for chronic Lyme disease is therefore different from the recommended treatment for acute Lyme by the IDSA which is, monotherapy with one antibiotic for example doxycycline. Again, similarities exist between HIV and chronic Lyme disease because both are treated with combination therapy.
The reason for combination therapy for HIV and chronic Lyme disease is however different. Combination therapy in HIV is motivated by the fact that the virus develops resistance to the medication if you only treat with one antiviral medication. For chronic Lyme disease, this is not the cases.
Combination therapy for chronic Lyme disease is motivated by the fact that the Borrelia bacteria changes morphology which means that monotherapy is not an effective treatment for Lyme disease. A serious Lyme disease infection should not be reduced to a simple cold. A better screening symptom for Lyme disease is paresthesia. Paresthesia manifests itself as vibrating sensation under the skin. The good thing is that the paresthesia stops when antibiotics have killed off the infection [ ] but also during treatment with antibiotics such as Metronidazole or Tinidazole.
There are three main questions that need to be answered to justify treatment for chronic Lyme disease. The answer to that question is yes [ , , , , ]. The answer to that question is yes according to our previous CDC reference.
There exist a few studies that show that the symptoms of chronic Lyme patients do not improve with antibiotics treatment. There exist at least two problems with these studies. Medical doctors should be able to use their professional expertise and in consultation with their patients determine the most appropriate treatment for patients. Such number was found by analyzing the performance of eight different Lyme disease tests.
The sample also included healthy controls. If a patient has had a blood test that suggests a Lyme disease infection that is fine, but a positive blood test should not be a requirement for a diagnosis. A person that suspect a Lyme disease infection is today, unfortunately, better of tossing a coin and diagnosing themselves because the blood tests for Lyme disease today will miss most infections. Specific antibodies often cannot be found in patients with Lyme disease because of the bacteria ability to shift its antigens.
Testing cerebrospinal fluid instead of blood will not improve test sensitivity because the bacteria can still shift its antigens in cerebrospinal fluid which means that the probability of detecting specific antibodies in cerebrospinal fluid is not larger than in blood. Moreover, cerebrospinal fluid causes the bacteria to change its morphology from a spirochete form to a cyst from [ ].
If you only diagnose Lyme disease in patients that have specific antibodies in their blood or cerebrospinal fluid, you will miss most cases.
We assume in Table 1 that the number of people in the disease and control groups are known and equal. In real life, however, we do not know the number of people in the disease and control group.
We can only observe the total number of people that tested positive in both groups. Number of people that tested positive in both groups z when the number of infected people in the disease group x and the number of healthy people in control groups y are known and assumed to be equal.
The number of people that tested positive in both groups z when the number of infected people in the disease group x and the number of healthy people in control groups y are unknown. The relationship between y, x and p can be seen in Figure 3. We now can adjust the equation for z and zz to include p as seen in Figure 4 and Figure 5. The number of people that tested positive in both groups z adjusted for the relationship between y and x p.
We can now solve for the number of infected people in the disease group x and the number of healthy people in the control group y when they are unknown given a value for z with matrix algebra as seen in Table 2.
We can algebraically manipulate the previous equations further as seen in Table 3. We can do some further modeling and plotting as seen in Table 4 , Figure 6 and Figure 7. The number of infected people in the disease group x given total number of people T and the relationship p between x and y. The number of healthy people in the control group y given the total number of people T and the relationship p between x and y.
The first limitation of this study is that we are using the incidence rate of Lyme disease from the USA on the population of Europe to get an estimate on how frequent Lyme disease is in Europe.
Using the incidence rate from the USA on the population of Europe is not optimal but unfortunately, our only choice since the ECDC do not have any data on Lyme disease. Lyme disease is not spread exclusively by vectors such as ticks. The second limitation of this study is that scientific literature that exists regarding Lyme disease as an STD is very limited.
Hence, the fact that the Borrelia bacteria can also or could also spread through sexual contact should not come as a surprise. Unfortunately, accurately modeling the spread of Lyme disease without sexual transmission is close to impossible because there are so many difficult questions that need to be answered regarding tick ecology [ ] for example in which geographic areas are ticks most frequent?
As I said, the epidemiological modeling becomes close to impossible especially for an economist maybe not for a biologist. All infectious diseases total number of infections in a population that are transmitted from person to person and where treatment is inadequate has by nature exponential growth over time.
Since the percentage change is constant over time, exponential growth models are also called constant growth rate models. For a linear growth model, the percentage change is decreasing over time.
The relationship between the transmission rate of an infection that is spread through sexual contact and the annual growth rate of infection can be seen in Table 5. We can see that given that each infected person has sex with one healthy person each year then the transmission rate is equal to the annual percentage growth rate of infection for an infectious disease that is spread sexually. To my knowledge, there does not exist any scientific literature regarding the annual growth rate of Lyme disease.
However, we can compare such number to other infectious diseases that are also spread through sexual contact such as HIV. The fourth limitation of this study is that the scientific literature regarding how successful IV treatment is at curing chronic Lyme disease is very limited.
However, the exact cure rate is not that important because we have known for a long time that antibiotics kill bacteria. The transmission rate for an STD and its relationship to the annual growth rate of infection. That number comes from a survey that was sent to seven of the largest commercial laboratories in the USA. The most interesting part of such publication an equation was not included in the article itself but was present in the supplementary data [ ].
The equation that the entire paper is based on is:. If we multiply the above equation by the number of individual Lyme disease blood tests that were performed in in the USA, then we get the observed number of Lyme disease infections in the USA in by the CDC. The CDC study estimated three different scenarios: high, low and average with an assumed test sensitivity of The other two are not reported in the paper and need to be calculated. Therefore, we can use our values for sensitivity and specificity.
The CDC calculations can be found in Table 6. We can see that the CDC has unrealistically and secretly assumed without motivation or explanation that the size of the control group with healthy people is 9 low scenario , 8. These assumed p -values cannot be empirically observed because it is impossible to know the value of p by simply looking at the total number of people that test positive in the control and disease group z.
Because blood testing today is so primitive you can more or less only test for one pathogen at the time and because the blood tests for Lyme disease are so insensitive most people today will only test to get a confirmation that they are infected.
Hence, many people will only test if they are infected. Such claim by the CDC, therefore, does not make any sense. Given the CDC unrealistic assumptions regarding se, sp and p, it appears that the equation is more or less correct.
The total number of Lyme disease infections that we can expect in the USA from to is The plots are presented in Figure 9 , Figure 10 , Figure 11 and Figure Since the ECDC does not have any statistics on how frequent Lyme disease is in Europe, it is difficult to determine an exact figure for the number of Lyme disease cases in Europe in The estimated number of Lyme disease infections in Europe in is 2,, The total number of Lyme disease infections that we can expect in Europe from to is Given an annual population growth rate in Europe of 0.
The plots are presented in Figure 13 , Figure 14 , Figure 15 and Figure The estimated number of people suffering from chronic Lyme disease in in the USA and Europe depend on the assumption we make regarding the estimated cure rate for chronic Lyme disease treatment and on the assumption that everyone that develop chronic Lyme disease from to is still alive.
The last assumption is very uncertain because of how difficult it is today for chronic Lyme patients to get treatment. If 2,, people were infected with Lyme disease in Europe in and go undetected by the non-exist statistics what types of illnesses can Lyme disease patients be misdiagnosed with?
The commonality between these diseases is that there is currently no known cure. Before we can start to estimate costs for Lyme disease, we need to discuss the tax on disability benefits. We have previously estimated that the number of infections in the USA for is approximately 1 million. In Europe, that number is approximately 2. Currently, the treatment cost for IV antibiotics for chronic Lyme disease are paid by the individual and not by the government or insurance companies.
The cost for IV treatment in Europe could easily be twice as large because patients must travel a long way and stay at a hotel close to a specialized chronic Lyme disease clinic to get daily IV treatments with a butterfly needle. Sometimes people are even forced to sell their house to afford treatment. We assume that acute Lyme disease is treated with oral antibiotics for one month and that chronic Lyme disease is treated with IV antibiotics for six months or one year.
We can see in Table 11 and Table 12 that the estimated treatment cost for Lyme disease for for the USA is somewhere between 4. We can also see that the cost of treating acute Lyme disease with oral antibiotics for one month only represents 0. The cost of treating acute Lyme disease with oral antibiotics is so small that it barely has an impact on total treatment costs. The estimated total cost for the treatment of acute and chronic Lyme disease for the USA for The estimated total cost for the treatment of acute and chronic Lyme disease for Europe for We have so far only looked at treatment cost.
Many people are forced to leave their jobs due to the infection. So, the cost of lost personal income is also high. The financial cost for both the individual lost earnings from not working due to chronic Lyme disease and for the government lost tax revenues because chronic Lyme patients are not working and disability benefits for chronic Lyme disease patients are therefore significant.
We can now calculate the government cost for chronic Lyme disease for the USA and Europe for if governments do not finance treatment. The average annual wage rate in Germany represents the average annual wage rate for Europe. A website called disabilitysecrets. This amount is on par with the lowest monthly disability payment after taxed paid in Sweden which is 11, Swedish kroner [ ] which means that the minimum annual disability benefit after tax for Sweden is , Swedish kroner which as of October is approximately 13, EUR.
We will use the monthly Swedish disability payment to represent the disability payment in Europe. We can see in Table 13 and Table 14 that the estimated lost personal income for chronic Lyme patients that are not working for for the USA is If the governments in the USA and Europe do not finance IV treatment with antibiotics for chronic Lyme disease, then the estimated government costs for chronic Lyme disease lost tax revenues because some chronic Lyme patients are not working plus disability benefits for chronic Lyme patients that not working for for the USA is We can also see that the government cost for chronic Lyme disease for which does not include treatment costs in the USA is 2.
In Europe, the government cost for chronic Lyme disease for is two times larger than the cost for six months of IV treatment in Europe for and the government cost is on par with the cost for one year of IV treatment in Europe for Government cost for chronic Lyme disease for the USA for if governments do not finance IV treatment with antibiotics for chronic Lyme disease.
Government cost for chronic Lyme disease for Europe for if governments do not finance IV treatment with antibiotics for chronic Lyme disease. We will again treat the cure rate for IV antibiotics for chronic Lyme disease as an unknown. Now we need to answer the important question: should a government pay for IV treatment for chronic Lyme disease? From a purely economic and financial perspective which excludes any ethical aspect of not offering antibiotics treatment to patients that suffer from a bacterial infection that can lead to death a government should finance treatment with IV antibiotics for chronic Lyme disease if.
Note also that the previous equation become less reliable over time. The closer we get to our endpoint which is the less impact the future government revenues and future government expenditures will have on a government's financial balance. Note that tax revenues from chronic Lyme patients that are not cured with treatment and working, saved disability benefits from chronic Lyme patients that are not cured with treatment and working, tax revenues from chronic Lyme patients that are sick and have not received treatment and are working and saved disability benefits from chronic Lyme patients that are sick and have not received treatment and are working are not included in the above government financial chronic Lyme disease balance sheet because they will be the same regardless of if the government choose to treat or not.
Independent and objective peer review is a critical component for scientific publication because of two main reasons. Scientific publication is not democratic in a sense that everyone including people without subject knowledge can vote and where the majority decides which papers are published. Such undemocratic nature of science is a strength, but it can also sometimes be a weakness.
Medicine is based on science, but medicine also has patients. It is therefore not unrealistic to expect that patients can influence decision making regarding their diagnosis and treatment. Unfortunately, today medical doctors, journal editors that desk reject papers, politicians, journalists and governments are experts when it comes to centralized decision-making.
It also appears that medicine and medical science today has become politicized where personal and subjective opinions govern. Government health agencies have not done an objective review of the scientific literature regarding chronic Lyme disease.
There exist at least five reasons for this. Encouraging physicians to do an independent and objective evaluation of the scientific literature is more important than to force physicians to blindly follow government treatment guidelines that may or may not be ethical and up to date. Doing scientific research and reading the scientific literature are demanding work. The importance of a patient voice is also something that is missing in the debate.
Doctors have a responsibility to help sick patients. To deny a patient medical treatment in a situation when there exists scientific evidence to support treatment will always be controversial. Infectious disease doctors need to be more modest here. Patients have a critical role in healthcare and without them, there will be no healthcare.
Some people conclude that since oral antibiotics cannot cure chronic Lyme disease patients, oral antibiotics should not be given to chronic Lyme patients. Such reasoning is a non-sequitur logical fallacy. HIV is a chronic infection that cannot be eradicated with oral medication, but HIV patients still receive oral medication for life.
Does there exist a general rule in medicine that states that only viral infections can become chronic? Is it ethical to refuse a patient treatment for an infection that can kill them without treatment? There also exist at least two problems with studies that treat chronic Lyme disease patients with IV antibiotics and conclude that such treatment did not eradicate the infection is 1 These studies usually treat chronic Lyme patients with monotherapy which is not a recommended treatment.
I also want to point out that a double-blind, randomized controlled trial where neither the patient nor the treating doctor knows if the patient has received placebo or medication might, in theory, sound like a good a way to determine how effective a certain medication is.
Reality is however far from theory. There also exists an ethical aspect. It is not ethical to give patients with a confirmed infection placebo in the name of science when such action could result in a lifelong infection for the patient. The estimated number of people that were infected with Lyme disease in the USA in is , If we assume that the incidence rate in the USA and Europe were the same, then approximately 2 million people were infected with Lyme disease Europe in Given an annual population growth in Europe of 0.
Most of these Lyme disease infections will, unfortunately, become chronic. I have also shown in this article that the financial implications of chronic Lyme disease are vast. A financial cost not only to patients but also to governments. Given that acute Lyme disease is treated with oral antibiotics for one month and chronic Lyme is treated with IV antibiotics for either 6 months or 1 year, then the estimated treatment cost for acute and chronic Lyme disease for for the USA is somewhere between 4.
The estimated lost personal income for chronic Lyme patients that are not working for for the USA is If the governments in the USA and Europe do not finance IV treatment with antibiotics for chronic Lyme disease, then the estimated government cost for chronic Lyme disease in the form of lost tax revenues because some chronic Lyme patients are not working plus disability benefits for chronic Lyme patients that not working for for the USA is The government cost for chronic Lyme disease which does not include treatment costs for in the USA is 2.
In Europe, the government cost for chronic Lyme disease for is two times larger than the cost for six months of IV treatment with antibiotics for Europe for and the government cost is on par with the cost, for one year of IV with antibiotics treatment for Europe for The cost for the governments of having chronic Lyme patients sick in perpetuity is very large.
Future government revenues and future government costs for chronic Lyme disease are however much more important to look at than historical annual cost. No one thinks that diseases that are caused by a virus should be treated with antibiotics but when people who need antibiotics for their survival do not get access to them, then there is something wrong.
If someone acknowledges that acute Lyme disease is caused by bacteria, then they are also forced by logical reasoning to acknowledge that chronic Lyme disease is caused by bacteria because the immune system by itself can never eradicate a Borrelia infection and a bacterial infection does not magically disappear without antibiotic treatment once a person has been infected. We have known for a long time that antibiotics kill bacteria. However, sometimes oral and even IV antibiotics are unable to eradicate a Borrelia infection, but those observations are irrelevant because HIV patients receive treatment for life even though antiviral medications cannot eradicate an HIV infection and people with chronic Lyme disease die without antibiotic treatment.
When a private special interest group such as the IDSA makes a political claim that three weeks of oral antibiotics is always enough to eradicate an acute or chronic Lyme disease infection, then the burden of proof lies with the IDSA.
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