On the mechanisms of conjugate vaccines PNAS

Hello /NBME,
This post will contain the answers to the Step 1 - NBME 24 Exam for educational discussion purposes. More info may be found here.
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Block 1

1. Enzymatic reaction labeled C
2. Increased serum testosterone concentration
3. Tyrosine
4. Probenecid
5. Thyroidal iodine uptake: decreased, Serum free triiodothyronine (FT3): increased, Serum free thyroxine (FT4): increased
6. Cigarette smoking
7. Artery of the ductus deferens
8. Sodium
9. HIV
10. Thiabendazole
11. X-linked recessive
12. Zidovudine
13. Renal tubular acidosis
14. Doxorubicin
15. Palms
16. Acute lung injury
17. Gluconeogenesis
18. Area labeled B (PCT) - A 7-year-old boy
19. Lateral pterygoid
20. ABO incompatibility
21. Pericardial tamponade
22. Injections of gonadotropins
23. Palpable right ventricular lift
24. Flexion at the distal interphalangeal joint
25. ACTH
26. Serum calcitriol: decreased, Serum parathyroid hormone: increased, Hematocrit: decreased
27. Catecholamine-mediated intracellular shifts of K+
28. Scar formation
29. Case-control study
30. Ruptured spleen
31. Phantom limb pain
32. Decreased movement through the arachnoid villi
33. Lamins
34. Factitious disorder imposed on another
35. CD8+ T lymphocytes
36. Intercostal
37. Annular pancreas
38. Irradiation with x-rays
39. Diabetes mellitus, type 1
40. Glycine and succinyl CoA
41. Vibrio parahaemolyticus
42. Metastatic carcinoma
43. The patient has another mutation that was not included in the previous analysis
44. Avoidant
45. Ingestion of undercooked meat
46. Spontaneous regression
47. Peptide transporter (TAP)
48. Escherichia coli
49. Proliferative glomerulonephritis
50. Succinylcholine

Block 2

1. Inter-endothelial gaps in venules
2. Generalized malabsorption
3. Migration
4. Regular exercise
5. One in four will have 25% B-globin function and may require occasional transfusions
6. Adductor brevis
7. Alveolar-arterial Po 2 difference
8. Failure of conversion of N5-methyltetrahydrofolate to tetrahydrofolate
9. Sotalol
10. Buccinator
11. Increased lymph flow
12. Heroin
13. Autoimmune adrenalitis
14. Aphthous ulcers
15. Both legal and ethical
16. Cardiac output: decreased, Left ventricular end-diastolic volume: increased, Stroke volume: decreased
17. Neural crest cells
18. Granulocyte-macrophage colony-stimulating factor
19. Cluster headache
20. Area labeled D (PICA)
21. Adenosine
22. Granulocyte colony-stimulating factor
23. Myositis ossificans
24. Hydrostatic pressure in Bowman space
25. Decreased afferent arteriolar resistance
26. Only cookies are independently associated with E. coli cases
27. Discuss further the impact of the patient's illness on the family
28. Beneficence
29. Right dorsolateral medulla
30. Peroxisomes
31. Post-translational modification
32. Extubate the patient and discontinue mechanical ventilation; make no attempt to do cardiopulmonary resuscitation in case of cardiac or respiratory failure
33. Tremor
34. Inhalant abuse
35. Diffuse pulmonary fibrosis
36. Posterior cerebral
37. HNPCC syndrome
38. Alkaline phosphatase
39. Neointima formation in the right coronary stent
40. Villous atrophy
41. Phase 3
42. Organic acid metabolism disorder
43. Unopposed alpha-adrenergic tone
44. Regulation of transcription
45. Pediculus humanus capitis
46. Intrauterine device
47. Delta-Aminolevulinate
48. Ureter
49. Phenylethanolamine N-methyltransferase
50. 25-hydroxyvitamin D: normal, Parathyroid hormone: decreased, Phosphate: increased

Block 3

1. G2
2. 0.05 < p < 1.0
3. Tuberculous osteomyelitis
4. Increased serum angiotensin II concentration
5. Pineal gland
6. Increased number of LDL receptors on hepatocytes
7. Normal ciliated columnar epithelium replaced by normal squamous epithelium
8. Hyporeflexia
9. Eosinophils
10. Respiratory acidosis
11. Defect in a cell membrane anchor protein
12. Ask the roommate not to smoke in the apartment
13. Intestinal mucosa
14. Determine whether the patient has decision-making capacity
15. Paroxetine
16. Alteration in DNA gyrase
17. Intraductal papilloma
18. Area labeled F
19. Discussion of the diagnosis with the patient privately
20. Formation of hypnozoites
21. 5%
22. Incarcerated inguinal hernia
23. Urine osmolality > plasma osmolality
24. Renal calculi in the left ureter
25. Decreased adherence
26. Ask the patient if she would allow the examination if her husband is present at all times
27. Borderline
28. Partial agonist at Beta-adrenergic receptors
29. Vincristine
30. Granulation tissue
31. Internal anal sphincter
32. Foramen cecum
33. Lungs
34. Stroke volume
35. This will typically resolve within the next 12 to 18 months.
36. Determination of erythrocyte sedimentation rate
37. Super rectal vein
38. Fixed cardiac output in spite of increased demand
39. 10%
40. Secreted by the proximal tubule
41. NADPH oxidase
42. Alendronate
43. Penile stimulation
44. 118/124 = 95%
45. Free radical formation
46. Nocturnal luteinizing hormone pulses
47. Monosodium urate
48. Misoprostol
49. Basal keratinocyte, suprabasal keratinocyte
50. Lunate

Block 4

1. Pulmonary capillary leakage
2. Atherosclerosis - A 75-year-old man
3. Area labeled E (Cerebellum, posterior lobe)
4. Adenine
5. Damage to the rectovaginal septum
6. Pulmonary capillary wedge pressure: increased, Pulmonary vascular resistance: decreased, Systemic vascular resistance: increased;
7. Oxygen saturation
8. Human papillomavirus
9. Decrease in intracellular ATP concentrations
10. Systemic vascular resistance: increased, Cardiac output: decreased, Pulmonary capillary wedge pressure: increased
11. Decreased blood volume
12. Synaptobrevin
13. Nucleoside reverse transcriptase inhibitor
14. Polysaccharide protein conjugate vaccine
15. 20
16. Endoplasmic reticulum
17. Case series
18. Negative-stranded RNA
19. Polyneuropathy
20. Area labeled B (PCT) - A 40-year-old woman
21. Somatostatin
22. E
23. Black fly
24. Muscle biopsy
25. Leucovorin
26. Coronavirus
27. Endochondral ossification
28. Infiltration of lymphocytes and monocytes
29. Conjugation
30. Presenilin
31. Tongue
32. Intracellular and extracellular dehydration
33. Increased synthesis of LDL receptors
34. 16%
35. Epstein-Barr virus-induced brain lymphoma
36. Serum gastrin
37. Persistent activation of voltage-gated Na+ channels in the nociceptor
38. Bronchopulmonary dysplasia
39. Normal aging
40. Inferior mesenteric and superior mesenteric
41. Atherosclerosis - A 65-year-old woman
42. Fusion of the sclerotomes
43. Factitious disorder
44. Increased hepatic production of T4-binding globulin
45. Competitive inhibitor
46. Parasympathomimetic stimulation
47. Ovarian Sertoli-Leydig cells
48. Transforming growth factor-Beta
49. Neuroendocrine cell
50. Lower motoneurons

Two problems not commonly discussed prior to the novel Coronavirus outbreak are the emergence of infectious disease and the related increasing prevalence of antimicrobial resistance. Here, I will explain the science behind these problems and some solutions that can be driven by legislation. My background is more squarely rooted in the science, so I apologize if I lean too heavily in this area as opposed to the economics and policy focus of this subreddit. I frequent this sub and enjoy the discourse here, and in my area this is one topic that overlaps with public health policy that I am passionate about.
To understand emerging disease and antimicrobial resistance, it’s important to understand evolution
The novel coronavirus, SARS-CoV2, is an example of an emerging infectious disease. SARS-CoV2 is a disease that, prior to 2019, had not to the best of our knowledge infected a human being. The genetic makeup of the virus indicates that the virus is natural, originating likely as a bat or pangolin Coronavirus that acquired the ability to infect humans, and that it is not man-made (1). Why do new diseases come into existence? Why haven’t humans encountered all the diseases capable of infecting us? Furthermore, why do diseases that we had previously thought conquered have the newfound ability to harm us again, in spite of our advancements in antibiotic development?
The answer to these questions is partially answered by evolution. Several novel viruses, like SARS-CoV1, MERS, and SARS-CoV2, began as zoonosis: infection by a pathogen with an animal source. Viruses, though generally considered non-living, contain nucleic acid genomes (either RNA or DNA) similar to every other organism in the tree of life. This genome is subject to selective pressures, just as with every other nucleic-acid containing being, and mutates non-specifically (that is, an organism develops a mutation, then selective pressures have a positive, negative, or neutral effect on retaining or discarding the mutation). An animal coronavirus that recognizes surface molecules on animal cells that have some similarity to human cell surface molecules may only be a few small genome changes away from being capable of infecting humans. It is likely that SARS-CoV2 emerged in one of two ways: as either an animal virus that mutated within an animal that gained the ability to infect humans, or as an animal virus that jumped to humans, and within the human host was selected for the ability to infect humans (1). The advent of novel viruses is also facilitated by the horizontal transfer of genetic material between distinct viral lineages. In Influenza viruses, this can take the form of segments of genome being transferred wholesale between viruses. Influenza viruses contain a genome composed entirely of RNA in multiple segments of sequence. Segments “re-assort” when flu viruses of distinct lineage infect the same cell, and viral genomes are mixed during the process of producing new viruses. Alternatively, as would be the case in coronaviruses, recombination occurs through a mechanism not fully understood, where whole portions of genome are exchanged between viruses (2).
The problem of antimicrobial resistance is also best understood through evolution. To explain this phenomenon, I will describe mainly how resistance manifests in bacteria, but similar processes drive resistance to anti-virals, anti-fungals, and anti-parasitics. Antibiotics are largely derived from natural sources: as microbes compete for resources, there is a drive to reduce competitors numbers by killing them or inhibiting their growth. Antibiotics are typically small molecules that target essential processes for bacterial growth; commonly cell wall biosynthesis (preventing growth and division of the cell, an example being penicillin), protein synthesis (blocks the process of translation, an example being erythromycin), production of RNA (blocks the process of transcription, an example being rifampin) or production of DNA (blocks the process of replication, an example being fluoroquinolone). These antibiotics arose through selective pressures, and in response bacteria have developed systems to circumvent the deleterious effects of antibiotics. These include: rapidly excreting the antibiotic before it is capable of inhibiting growth (efflux pumps, a notable offender being Pseudomonas aeruginosa, a common pathogen in patients with cystic fibrosis), degrading the antibiotic (beta-lactamases are a class of enzyme that degrade beta-lactam family antibiotics, such as penicillin), modifying the antibiotic (the most common mechanism for aminoglycoside resistance is to chemically modify the antibiotic so it doesn’t work), or simply modifying the target (Streptococcus pneumoniae is a microbe that causes multiple diseases that is naturally resistant to beta-lactams by modification of the drug target, the aptly-named Penicilin-binding protein) (3). As humans, it has been beneficial to identify these natural compounds and use them medically to treat infection.
Bacteria have incredible genome plasticity, engaging in a process known as horizontal gene transfer (HGT; sometimes referred to as lateral gene transfer) that increases the prevalence of resistant microbes. Not all bacteria are capable of this set of processes, but importantly several medically important pathogens, such as E. coli, Salmonella, Yersinia pestis, Acinetobacter baumannii engage in processes that facilitate the transfer of genetic material between bacteria. There are several molecular mechanisms for HGT: bacteria-infecting viruses can transmit pieces of genetic material between similar bacteria (transduction), bacteria can form a bridge that transfers plasmids (conjugation; plasmids are typically circular pieces of DNA, and are typically maintained independently of the bacterial chromosome and commonly encode antibiotic resistance genes), or bacteria can simply pick up naked DNA in the environment and integrate that DNA into their chromosomes (natural transformation) (3). The effect of these processes is that, when a gene that imparts resistance to a particular antibiotic is introduced into a population, it may spread between members of the population, not just within the progeny of the cells that encode the resistance gene. This is especially true when a gene that imparts resistance is on a plasmid or is otherwise mobilizable (transposons, or jumping genes, are also common perpetrators of transmission in that they move somewhat readily and often encode drug resistance). The key point to understand here is that while genes are present in bacteria, either on a chromosome or on a mobilizable element, these genes are capable of moving to many other members of the same population.
To understand this in more practical terms, many people have undergone a course of antibiotics and experienced gastrointestinal distress or stomach pains. This can be attributed to disturbing your normal intestinal microbiome, as you kill off non-resistant bacteria. Now assume you have an infection of some sort, it could be anywhere in your body accessible to an orally administered antibiotic, and your doctor prescribes you an antibiotic. It is possible, and possibly probable, that within your gut are bacteria that harbor resistance genes. In the absence of the antibiotic, these are likely to have a neutral or possibly deleterious effect; think of this like a welder that is unable to remove his welding mask: it certainly helps when he is welding, but is cumbersome at other times of the day. Taking the antibiotic results in high selection for resistant microbes to grow and prosper. This allows the resistant bugs to soon outnumber the non-resistant bugs. Ultimately, this increases the concentration of the resistance genes in the population of microbes in your gut. Subsequent to this, you may encounter an infection of a gastrointestinal pathogen that, in infecting your gut, acquires the resistance genes that you selected for. In disseminating this pathogen, you are also disseminating this resistance gene. Additionally, and perhaps more importantly, in taking antibiotics you select for drug resistance in the opportunistic pathogens of your body, notably Clostridium dificile and Staphylococcus epidermidis. These microbes are capable of causing disease, but reside in you or on you and cause infection when conditions are optimal for their growth.
The problem of antimicrobial resistance is convergent with emerging pathogens, as many pathogens “re-emerge” as they develop resistance to antimicrobials. While TB cannot be said to be an emerging pathogen as the world has been experiencing a TB pandemic since at least the early 1800’s, TB is re-emerging in the since that increased drug resistance has led to strains of TB that are not treatable via the traditional course of antibiotics (4). Similarly, common pathogens such as E. coli, Klebsiella, and Clostridium dificile are bugs that have become increasingly resistant to the antibitoics used to treat them (5). Acinetobacter baumanii, a soil microbe with resistance to a spectrum of antibiotics, became a common Gulf and Iraq War wound infection. Many of these pathogens find a home in hospitals, where the use of antibiotics is prevalent and potential hosts are abundant. Furthermore, the recently emerged pathogen HIV, the causal agent of AIDS, is intersectional with that of antibiotic resistance, as infection with HIV increases susceptibility to bacterial infections due to reduced immune cell numbers; increased infection rates of Both issues, antibiotic resistance and emerging pathogens, pose a threat to human health the world over, and I will attempt to address both of these issues in this post.
The problem of emerging disease and antibiotic resistance is exacerbated by humans
To what extent do emerging diseases and antibiotic resistance affect humans? SARS-CoV2 has had an extensive impact on human health and living, and the response to shut down to stop the spread of the virus has had a large economic impact. It is impossible to accurately predict the threat posed by non-discovered viruses, so the next threat could be relatively benign, or truly horrific. This is not to fearmonger, there is no reason to suspect that such a virus is bound to steamroll us soon, but to say that the next plague may be brewing inside a pig in a Chinese farm or outside our homes in the bodies of ticks, and we would not know it. The US Center for Disease Control and Prevention (CDC) has published two Antibiotic Resistance Threat reports on the subject, in 2013 and 2019. In the 2013 edition, it was reported that 2 million people in the United States will acquire an antibiotic resistant infection, and that 23,000 will die as a direct result of that infection (5). While by 2019 this was realized to be an underestimation of the drug-resistant cases, new approaches had determined that the true value had lowered from 2013 to 2019, with an updated estimate of 2.8 million cases and 35,000 fatalities in 2019 (6). An excellent illustration of the problem can be found on page 28 of the 2013 report, which reports the introduction date (left) and the date at which resistance was observed on the right for crucial antibiotic groups. Commonly, within a decade of the introduction of an antibiotic, resistance emerges. This problem cannot be expected to go away on its own, and more than likely pathogens commonly thought vanquished will re-emerge with drug-resistant characteristics.
There are human processes that contribute to the emergence of disease and spread of antibiotic resistance. In China, Wet Markets bring together livestock from all over the country, creating an environment that is diverse in the microbial life that live commensally and parasitically in and on these animals. The proximity of these animals allows for the exchange of these microbes; these microbes are then capable of exchanging genetic material. As I described for Flu and Coronaviruses, viruses that come into contact within cells are capable of genetic recombination, a process that can result in viruses that are capable of infecting humans. This is not to say this is a common phenomenon, just that 1) the process is accelerated by live animal markets and 2) this practice and resulting genetic recombination of zoonotic viruses is thought to have contributed to both the original and novel SARS-CoV outbreaks.
In the United States, a textbook example of an emerging disease is Lyme Disease (7). Named for the town of Lyme, Connecticut, Lyme Disease is caused by the peculiar bacterium known as Borellia burgdorferi. Borellia is a corkscrew-shaped bacteria that is interesting for its ability to grow without iron (a key component of the immune response is the sequestration of iron away from pathogens). Lyme Disease is spread through ticks, and the number of infectious cases is exacerbated by reforestation and settlement close to wooded areas in suburban environments. As building projects move closer to forested areas, exposure to arthropod-borne illnesses will be expected to rise.
Beyond settlement and the wet market practice, the emergence of new infectious disease is complicated by global warming and healthcare practices. Global warming is hypothesized to drive heat resistance in fungi, potentially improving their capacity to grow within the human body (8). The pathogenic potential of fungi is hypothesized to be limited by the heat of the human body, and there is some speculation that global warming is a contributing factor to the emergence of the notorious fungal pathogen Candida auris (8). These claims should be taken with a grain of salt and evaluated critically, but it is possible that human-caused climate change will disturb the ecology of our planet with as of yet unforeseen consequences, among them the generation novel and resurgent diseases.
In healthcare, over-prescription of and a lack of regulation on antibiotics has caused the problem to worsen (5,6). When a patient receives an antibiotic, the drug has an effect on all microbes where the drug is bioavailable. This includes the intestines, which contain a resident population of microbes, and the skin, which contains Staphylococci resident species that prevent colonization by pathogenic strains of similar bacteria. These residents are then selected for their ability to resist the drug, causing an increase in resistance among the healthy microbiota. These resistance genes, as I have described, can then move between dissimilar bacteria in the same environment. If a harmful strain of E. coli is introduced into such an environment, for example, it has a higher likelihood of encountering and assimilating the genetic potential to resist antibiotics than in an environment that is naïve to the antibiotic. Patients are commonly prescribed antibiotics for infections that are more likely to be caused by a virus, or in instances where an infection is likely to run course without medical intervention. The increased exposure to antibiotics causes the microbiota to increase the concentration of resistance genes. Additionally, in places like India, the regulations on antibiotics are much more laxed than even the United States, where one is able to purchase over-the-counter antibiotics. This allows anyone to give themselves an incomplete course of antibiotics for any condition, even if the symptoms are not caused by an infection of any kind. Additionally, prescription antibiotics that have deteriorated with time, or are manufactured with subpar quality control resulting in lower concentrations, that remain in circulation exacerbate the problem by establishing sub-inhibitory concentrations of the antibiotic in the body and resulting in selection for resistance. Furthermore, environmental pollution of antibiotics into natural water sources and sewage results in increased environmental concentrations of resistance genes. These genes can spill into humans by exposure to microbes in these environments (9).
Agriculture provides another increase in the concentration of resistance genes (10). Livestock are fed antibiotics, which increase the weight of animals in an as-of-yet not understood mechanism. A deleterious consequence of this increase in yield with antibiotic usage is the increase in resistance in response to this widespread antibiotic usage. These resistance genes then find their way into humans, whether through ingestion of food contaminated with resistant microbes.
Science and technology can solve the problem, but face institutional and biological challenges
There are both institutional and scientific challenges to combating emerging disease and antibiotic resistance. Some of these problems are easily apparent as I have described above: countries with laxed restrictions on who can obtain antibiotics, countries where the drugs are used often over-prescribed, suburbanization, and global warming all contribute to the problem.
Scientifically, there are challenges in that novel diseases are difficult to combat. The novel Coronavirus had the precedent of other coronaviruses (i.e. SARS and MERS) that had been studied and their virology dissected, but that won’t necessarily be the case everytime a novel pathogen infects a human. A technological benefit to this problem is the use of meta-genomics, which allows for DNA/RNA sequencing without prior knowledge of the nucleic acid sequence of the genome. Within weeks of the first identification of the virus, its sequence was available to researchers. This was not the case during the outbreak of SARS-CoV1, when meta-genomics approaches such as Illumina Sequencing, NanoPore Sequencing, and Pacific Biosciences Sequencing were not available. In the event of a novel disease emergence, this information would be vital to combating the pathogen.
Despite not knowing necessarily what the next threat will be, expanding the human knowledge base on microbes is an essential component of any plan to fight emerging diseases. Any emerging disease is likely to be similar to other microbes that we have encountered, and knowledge of the physiology of these organisms helps to understand weaknesses, transmission, and potential therapeutic targets. The study of all microorganisms therefore benefits the effort to combat the next pandemic, as any one piece of information could be critical.
Surveillance is perhaps the most important tool to fight emerging infectious disease; knowing the problem exists is a crucial step to curbing spread. A recent example of successful surveillance can be seen in a recent PNAS publication regarding the presence of potential pandemic influenza in hogs, and the presence of antibodies against this particular class of flu viruses in swine workers (11). While at present it does not appear that the virus has acquired the ability to cause a pandemic, this knowledge allows for immunologists to potentially include viral antigens specific to this particular viral class in seasonal vaccines. Surveillance is critical in controlling both emerging diseases and antibiotic resistance: knowledge of what potential pathogens emerge where, and what microbes are exhibiting resistance to what drugs, can drive containment and treatment efforts.
To combat antibiotic resistance, new drugs must be developed, but there are hurdles in identification, validation, and production of new antibiotics. First, potential new antibiotics have to be either identified or designed. This often involves looking through filtered environmental samples to determine the presence of small molecules that inhibit bacterial growth, or chemically altering known drugs to circumvent drug resistance. This is not necessarily difficult, as there are microbes in the soil and water that produce potential therapeutics, but this does require both time and money, as well as the consideration that it is likely that resistance to that novel therapeutic exists in the environment from which it was pulled. New drugs must be safe, but due to the abundance of antibiotics presently in use and their historic efficacy, the standard for antibiotics to pass safety regulations is extremely high. As drug resistance becomes more common, it will become apparent that more and more side effects may have to be tolerated to prevent death due to bacterial infection. Finally, and the most important challenge to developing antibiotics is that the profit margin on antibiotics is low for drug companies in the present market, disincentivizing research and production of novel drugs.
In addition to stand-alone antibiotics, new inhibitors of resistance must be developed as well. Clavulanic acid is one such inhibitor, and is administered with the beta-lactam drug amoxicillin to improve its ability to kill bacteria. Bacteria that are resistant beta-lactams often encode enzymes called beta-lactamases. Beta-lactamases break open the active portion of the beta-lactam molecule, rendering it ineffective in attacking its target. Clavulanic acid is a beta-lactam itself, and is a target for the beta-lactamase enzyme; however, when the enzyme begins to degrade clavulanic acid, the enzyme becomes stuck at an intermediate step in the reaction, rendering the beta-lactamase enzyme useless. These drugs must also be explored and screened for in environmental samples, as well as developed. It is possible to take a rational approach to drug design, with increasing knowledge of how resistance mechanisms work. This means that scientists specifically look at, say, a beta-lactamase enzyme at the molecular level, and design a small molecule that will fit into the enzyme and block its function. Chemists then design the molecule to test its efficacy.
Ultimately, scientists either know how to solve the problem, or know how to get the tools they need to solve the problem. It is the institutional challenges that make the problem more difficult to solve.
How legislation can improve the ability of scientists to combat emerging disease and drug resistance
In discussing emerging diseases and antibiotic resistance, I try to draw parallels to the problem of global warming: a global problem with global solutions. I don’t have a novel solution to climate change to discuss here, other than to parrot this subreddit’s typical ideas, so I will omit that discussion here. That is to say, global warming is a driver for emerging infectious disease, and fighting global warming is important to combat the potential rise of fungal pathogens. I will, however, discuss some ideas for combating emerging disease and drug resistance. These ideas are mostly derived from scientists familiar with the problem,
Funding for research, basic and applied, is crucial. No bit of knowledge hurts in the fight against human disease. Learning how Alphaviruses replicate, determining the structure of E. coli outer membrane proteins, and examining the life cycle of the non-pathogen Caulobacter crescentus all contribute to the fight against the next disease. The more we know, the more powerful our vision is in understanding the inner machinations of disease. Every immune response, every molecular mechanism, and every aspect of microbial physiology is potentially a drug or vaccine target, a clue into pathogenesis, or an indication of how a bug is likely to spread. The Trump administration has not been kind to science funding (12). Science that does not appear to have benefit at first glance often does in the long run, and for this reason I will stress the importance of funding research of this sort, as well as funding applied research.
Knowing is half the battle. In combating emerging diseases, it is important to know they exist. As I have mentioned the example of recent viral surveillance with regard to the novel reassortment influenza viruses, I would like to stress the importance of funding surveillance programs in fighting emerging disease and drug resistance. There are currently US governmental surveillance programs that provide valuable information about the spread of drug resistance, such as NARMS in the United States (13).
In the United States, there is a need for greater accountability in using antibiotics. Resistance is unlikely to completely go away, even when the use of an antibiotic is discontinued, but the levels of resistant bacteria dwindle when the selective pressure is reduced. For this reason, several medical practitioners have proposed a rotating schedule of prescription antibiotics, that includes the retention of some new antibiotics from use. The reasoning for this is that, in the years following the halted use of a particular antibiotic, it is expected that the concentration of resistant bacteria will decrease. As I discussed with the example of always wearing a welding helmet, carrying resistance genes often imparts some form of growth defect on the resistant bacteria (for example, altering an essential gene targeted by an antibiotic may render the bacteria resistant, but there is a reason such a gene is essential, in that it’s required for growth; changing the gene in a substantive way may negatively impact its performance and by extension make these resistant bacteria less fit). A rotating cycle of what antibiotics are allowed to be prescribed, informed by surveillance data, would buy time for the development of new antibiotics as well. Additionally, higher standards should be required for the prescription of antibiotics, to increase accountability of physicians; these standards could involve clinically verifying the presence of susceptible bacteria prior to administering a drug in situations where the disease in not life-threatening.
There is a need to reduce the environmental pollution of drugs into sewage and natural bodies of water as well. This will require research into cost-effective methods for reducing the population of resistant bugs and drugs in these environments. In the case of natural bodies of water, a source of contamination is often factories where drugs are produced. Often, waters near these factories have high levels of antibiotics that select for resistance to develop and spread. This may require legislation to improve environmental outcomes, as well as surveillance of drug resistance gene levels and the levels of antibiotics in these waters to ensure compliance.
There is also a need to halt the use of antibiotics in treating livestock (14). Halting the use of antibiotics typically results in reductions of antibiotic resistant bug populations within a year or two (10). I don’t know of studies that estimate the economic cost of halting use of antibiotics in American meat, but in the case of Denmark, livestock production does not appear to have been significantly impacted.
I think that the most challenging problem will be for drug companies to develop new antibiotics when there is not presently a financial incentive to do so. Because antibiotics are still largely effective, and the financial benefit to adding an antibiotic to the market does not outweigh the cost to put a drug to market, there is not currently a large incentive to produce new drugs (15). To address this negative externality, it is necessary to generate financial incentives of some form for the production of new antibiotics. This may take the form of subsidizing antibiotic discovery efforts and drug safety trials; additionally, applied research with the goal of specifically finding new antibiotics should see increased funding.
To combat the problem overseas, it is obvious that obtaining an antibiotic course must occur through a doctor. This eliminates false self-diagnoses of bacterial infections. The problem of wet markets may be partially resolved by preventing animals that do not regularly contact each other from being traded and stored in the same vicinity as animals that are not typically encountered. This may involve limiting a particular wet market to the trade of animals that come from a particular geographic area, preventing geographically diverse microbes from encountering each other.
It's on all of us to stop the next pandemic:
If you made it this far, thank you reading this post and I hope that I have convinced you of the importance of this issue! There are simple steps that we can all take as consumers to reduce antimicrobial resistance: don’t take antibiotics unless prescribed by a doctor and buy meat that was produced without antibiotics. I welcome any and all criticism, and would love to hear people's ideas! Please let me know of any errors as well, or any missed concepts that I glossed over. I've been excited to give my two cents to this sub, and I don't want to mislead in any way.
Sources:
1: Andersen, KG, et al. 2020. The Proximal Origin of Sars-CoV-2. Nature Medicine 26: 450-452.
2: Su, Shou, et al. 2016. Epidemiology, Genetic Recombination, and Pathogenesis of Coronaviruses. Cell Trends in Microbiology 24(6): 490-502. https://doi.org/10.1016/j.tim.2016.03.003
3: Munita, JM; Arias, CA. 2016. Mechanisms of Antibiotic Resistance. Microbiology Spectrum VMBF-0016-2015. doi:10.1128 /microbiolspec.VMBF-0016-2015.
4: Shah, NS; et al. 2007. Worldwide Emergence of Extensively Drug-resistant Tuberculosis. Emerging Infectious Diseases 13(3): 380-387. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2725916/
5: CDC Antibiotic Threats Report, 2013. https://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf
6: CDC Antibiotic Threats Report, 2019. https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf
7: Barbour, AG; Fish, D. 1993. The Biological and Social Phenomenon of Lyme Disease. Science 260(5114):1610-1616. https://pubmed.ncbi.nlm.nih.gov/8503006/
8: Casadevall, A; Kontoyiannis, DP; Robert, V. 2019. On the Emergence of Candida auris: Climate Change, Azoles, Swamps, and Birds. mBio 10.1128/mBio.01397-19. https://mbio.asm.org/content/10/4/e01397-19
9: Kraemer, SA; Ramachandran, A; Perron, GG. 2019. Antibiotic Pollution in the Environment: From Microbial Ecology to Public Policy. Microorgansims 7(6): 180. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6616856/
10: Levy, S. 2014. Reduced Antibiotic Use in Livestock: How Denmark Tackled Resistance. Environmental Health Perspectives 122(6): A160-A165. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4050507/
11: Sun, H, et al. 2020. Prevalent Eurasian avian-like H1N1 swine influenza virus with 2009 pandemic viral genes facilitating human infection. Proceedings of the National Academy of Science https://doi.org/10.1073/pnas.1921186117.
12: Kaiser, J. 2020. National Institutes of Health would see 7% cut in 2021 under White House plan. Science Magazine. https://www.sciencemag.org/news/2020/02/national-institutes-health-would-see-7-cut-2021-under-white-house-plan
13: About NARMS: National Antimicrobial Resistance Monitoring System for Enteric Bacteria. https://www.cdc.gov/narms/about/index.html
14: Khachatourians, GG. 1998. Agricultural use of antibiotics and the evolution and transfer of antibiotic-resistant bacteria. CMAJ 159(9):1129-1136 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1229782/
15: Jacobs, Andrew. 2019. Crisis Looms in Antibiotics as Drug Makers Go Bankrupt. The New York Times. https://nyti.ms/366f7it

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Exploring the Boundaries of Environmental and State-Corporate Crime in Bolivia, Peru, and Mexico(self) 1 [Book] International Human Rights Law (3rd edn) Edited by Daniel Moeckli - Oxford University Press(self) 4 [Book] Participatory Heritage, Edited by Henriette Roued-Cunliffe , Andrea Copeland(self) 4 [BOOK] Political Representation in Southern Europe and Latin America Before and After the Great Recession and the Commodity Crisis - André Freire, Mélany Barragán, Xavier Coller, Marco Lisi, Emmanouil Tsatsanis(self) 4 [BOOK] Latin America and Policy Diffusion From Import to Export - Osmany Porto de Oliveira, Cecilia Osorio Gonnet, Sergio Montero, Cristiane Kerches da Silva Leite(self) 0 [Book] Sexual behaviour in Britain: The National Survey of Sexual Attitudes and Lifestyles (1994)(self) 1 [book] Studien zur Hirnpathologie und Psychologie - Pick, Arnold(self) 4 [Other] Special Issue, Blockchain innovation and public policy, Journal of Entrepreneurship and Public Policy: Volume 9 Issue 2(self) 4 [BOOK] baby jails: the fight to end the incarceration of refugee children in america/ jstor account??(self) 1 [Journal] Special Issue: Blockchain innovation and public policy, Journal of Entrepreneurship and Public Policy, Volume 9, Issue 2(self) 1 [Book] Blackstone's EU Treaties and Legislation 2019-2020 (20th ed)(self) 3 [article] Deep Graph Kernels(self) 5 [Book] Routledge Handbook of the South Asian Diaspora - By Joya Chatterji, David Washbrook(self) 4 [Book] Growth and distribution(self) 1 [BOOK] The Radical Left in Europe in the Age of Austerity - Babak Amini(self) 4 [Book] Political Myth by Christopher Flood (Routledge) (2002)(self) 2 [Article] Robotic Assisted Radical Cystectomy vs Open Radical Cystectomy: Systematic Review and Meta-Analysis + Niranjan J Sathianathen et al(self) 1 [Book] Folk Art Potters of Japan Beyond an Anthropology of Aesthetics (Routledge) by Brian Moeran(self) 1 [book] Revolution: How the Bicycle Reinvented Modern Britain(self) 5 [BOOK] Radical Left Movements in Europe - Magnus Wennerhag, Christian Fröhlich, Grzegorz Piotrowski(self) 4 [BOOK] Party System Change, the European Crisis and the State of Democracy - Marco Lisi(self) 5 [BOOK] Routledge Handbook of Contemporary European Social Movements. Protest in Turbulent Times - Cristina Flesher Fominaya, Ramon A. Feenstra(self) 4 [Book] Attorney-Client Privilege in International Arbitration(self) 1 [Article] An Alternative Ontology of Food Beyond Metaphysics by Lisa Heldke. Published in Radical Philosophy Review, Vol 15, Issue 1, 2012(self) 1 [Book] Bello, Walden 2005 Dilemmas of Domination: The Unmaking of the American Empire. Zed Books, 2005.(self) 1 [Article] Owning the PastOwning the Past Reply to Stokes(self) 1 [Article] Owning the PastOwning the Past Reply to Stokes(self) 1 [Book] McQuire, Scott. Crossing the Digital Threshold. 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Acute disseminated encephalomyelitis secondary to serogroup B meningococcal vaccine
Acute disseminated encephalomyelitis (ADEM) is rare in adults. This is the first published case of ADEM secondary to serogroup B meningococcal vaccine. Vaccination must be considered in the differential diagnosis of ADEM.” https://www.ncbi.nlm.nih.gov/m/pubmed/27772786/
Acute flaccid paralysis surveillance indicators in the Democratic Republic of Congo during 2008-2014.
“Of the 13,749 AFP cases investigated, 58.9% received at least three doses of oral polio vaccine (OPV), 7.3% never received OPV, while the status of 18.3% was unknown.” https://www.ncbi.nlm.nih.gov/m/pubmed/27642491
Acute maternal anterior poliomyelitis in a non-endemic zone
“The authors report the case of a 26 year old woman with acute anterior poliomyelitis contracted during the vaccination of her baby. Despite having been herself vaccinated in infancy she was not protected against the poliovirus. The clinical interest of this uncommon case is a severe paralytic state with definitive paraplegia.” https://www.ncbi.nlm.nih.gov/m/pubmed/2561040/
Acute Onset of Parkinsonism with Reversible Course After H1N1 Vaccination: Insight From a Young Lady
Parkinsonian symptoms can be induced by acute encephalitis, syphilis, malaria, poliomyelitis, and sudden carbon monoxide poisoning.1,2 In this report, a 17-year-old girl had Parkinson’s disease (PD) symptoms after a flu shot. So far, this is the first vaccine-related disorder that mimics PD.” http://neuro.psychiatryonline.org/doi/pdf/10.1176/appi.neuropsych.11110324
Adjuvants- and vaccines-induced autoimmunity: animal models.
“In some cases, adjuvants may trigger generalized autoimmune response, resulting in multiple auto-antibodies, but sometimes they can reproduce human autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus, Sjögren syndrome, autoimmune thyroiditis and antiphospholipid syndrome and may provide insights about the potential adverse effects of adjuvants.” https://www.ncbi.nlm.nih.gov/m/pubmed/27417999
Administration of aluminium to neonatal mice in vaccine-relevant amounts is associated with adverse long term neurological outcomes.
Our previous ecological studies of autism spectrum disorder (ASD) has demonstrated a correlation between increasing ASD rates and aluminium (Al) adjuvants in common use in paediatric vaccines in several Western countries https://www.ncbi.nlm.nih.gov/m/pubmed/23932735/
Adverse effect versus quality control of the Fuenzalida-Palacios antirabies vaccine.
“We evaluated the components of the Fuenzalida-Palacios antirabies vaccine, which is till used in most developing countries in human immunization for treatment and prophylaxis. This vaccine is prepared from newborn mouse brains at 1% concentration. Even though the vaccine is considered to have a low myelin content, it is not fully free of myelin or of other undesirable components that might trigger adverse effects after vaccination. The most severe effect is a post-vaccination neuroparalytic accident associated with Guillain-Barré syndrome. https://www.ncbi.nlm.nih.gov/m/pubmed/10030074
Adverse events following Haemophilus influenza type b vaccines in the Vaccine Adverse Event Reporting System, 1990-2013.
“Includes 29 747 reports after Hib vaccines; 5179 (17%) were serious, including 896 reports of deaths. Median age was 6 months (range 0-1022 months). Sudden infant death syndrome was the stated cause of death in 384 (51%) of 749 death reports with autopsy/death certificate records.” http://www.ncbi.nlm.nih.gov/m/pubmed/25598306/
Aluminum hydroxide injections lead to motor deficits and motor neuron degeneration.
This ALS “cluster” represents the second such ALS cluster described in the literature to date. Possible causes of GWS include several of the adjuvants in the anthrax vaccine and others. The most likely culprit appears to be aluminum hydroxide. https://www.ncbi.nlm.nih.gov/m/pubmed/19740540/
Antibodies to human myelin proteins and gangliosides in patients with acute neuroparalytic accidents induced by brain-derived rabies vaccine.
Antibody responses to myelin antigens were analysed in 15 patients who developed acute neuroparalytic accidents (ANPA) during post-exposure rabies vaccination using a rabies vaccine prepared on brain tissues and in 30 individuals who were uneventfully vaccinated. https://www.ncbi.nlm.nih.gov/m/pubmed/9846820/
ANTIRABIES ANTIBODY RESPONSE IN MAN TO VACCINE MADE FROM INFECTED SUCKLING-MOUSE BRAINS.
“Antirabies vaccines produced from infected brains of adult mammals have always had the potentiality of causing post-vaccinal paralysis or allergic encephalitis in man. Attempts in recent years either to remove the paralytic factor from brain-tissue vaccines or to use as the virus source infected tissue other than nervous tissue (e.g., chick embryos) have usually resulted in a substantial reduction of the specific antirabies potency.” https://www.ncbi.nlm.nih.gov/m/pubmed/14163964/
An assessment of thimerosal use in childhood vaccines.
“Limited data on toxicity from low-dose exposures to ethylmercury are available, but toxicity may be similar to that of methylmercury. Chronic, low-dose methylmercury exposure may cause subtle neurologic abnormalities.” https://www.ncbi.nlm.nih.gov/m/pubmed/11331700
Association of acute cerebellar ataxia and human papilloma virus vaccination: a case report.
We report the case of a patient who developed symptoms of acute cerebellar ataxia (ACA) after administration of the human papilloma virus (HPV)-16/18 vaccine.
This patient developed symptoms of ACA, including nausea, vertigo, severe limb and truncal ataxia, and bilateral spontaneous continuous horizontal nystagmus with irregular rhythm, 12 days after administration of the HPV-16/18 AS04-adjuvanted cervical cancer vaccine.
This temporal association strongly suggests that ACA was induced by the vaccination.” https://www.ncbi.nlm.nih.gov/m/pubmed/23378179/
Behavioral abnormalities in female mice following administration of aluminum adjuvants and the human papillomavirus (HPV) vaccine Gardasil.
Vaccine adjuvants and vaccines may induce autoimmune and inflammatory manifestations in susceptible individuals. To date most human vaccine trials, utilize aluminum (Al) adjuvants as placebos despite much evidence showing that Al in vaccine-relevant exposures can be toxic to humans and animals. https://www.ncbi.nlm.nih.gov/m/pubmed/27421722/
Bell’s palsy as a possible complication of hepatitis B vaccination in a child.
Bell’s Palsy is the sudden onset of unilateral temporary paralysis of facial muscles, resulting from seventh cranial nerve dysfunction. Also, it is known that hepatitis vaccine is associated with Gullian-Barre Syndrome and demyelinating disease, possibly through an immune response mechanism (9–12,17). Therefore, it is at least theoretically possible that hepatitis B vaccines may trigger Bell’s Palsy through a similar mechanism https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2928079/
A case of Guillain-Barré syndrome following cholera vaccination (author’s transl).
“A 45-year-old woman developed bilateral ascending flaccid paralysis after cholera vaccination, 15 days after the first and 1 day after the second injection. The clinical course resulted in nearly complete paralysis of the lower limbs, paresis of the upper limbs and partial involvement of the cranial nerves. There was only slight sensory loss. The CSF revealed no pleocytosis and a protein level of 206 mg/100 ml. https://www.ncbi.nlm.nih.gov/m/pubmed/50424/
Case report of post sheep brain rabies vaccine neuroparalytic complications at Tikur Anbessa Teaching Hospital, in Ethiopia.
“We report four cases of ascending paralysis admitted to Tikur Anbessa Specialized Hospital (TASH) within six months period between December 2010 and June 2011 following administration of sheep brain tissue anti rabies vaccine for presumed rabies exposure. The paralysis started after a minimum of twelve doses of the vaccine. Two of the patients were discharged with severe paralysis and two died in the hospital.” https://www.ncbi.nlm.nih.gov/m/pubmed/23409403/
Complications of pertussis immunization (author transl).
“16 cases of neurological disease and/or death shortly after pertussis immunization are reported. Eight patients had convulsions, six with ensuing permanent defects. Severe polymyositis was observed in one case. Five infants died 12 h to 4 days after vaccination: two after acute encephalopathy and three in the form of a sudden unexpected death (SID). In two fatal cases the morphological changes in the brain corresponded to those of pertussis encephalopathy: neuronal degeneration in various parts of the cortex, especially in the region of the ammons horn, and in the cerebellum. https://www.ncbi.nlm.nih.gov/m/pubmed/18670/?
A comprehensive review of mercury provoked autism
Mercurials may be found in drugs for the eye, ear, nose, throat, and skin; in bleaching creams; as preservatives in cosmetics, tooth pastes, lens solutions, vaccines, allergy test and immunotherapy solutions; in antiseptics, disinfectants, and contraceptives; in fungicides and herbicides; in dental fillings and thermometers; and many other products https://www.ncbi.nlm.nih.gov/m/pubmed/19106436/
Demyelinating disease and polyvalent human papilloma virus vaccination
“Since its inception, the polyvalent vaccine against the human papilloma virus (HPV), Gardasil, has generated some controversies as a temporal relationship between the administrations of the vaccine and the development of a few autoimmune diseases, such as acute disseminated encephalomyelitis (ADEM), multiple sclerosis (MS) and Guillain–Barre syndrome have been reported.1–3 We encountered two cases whose initial presentation of CNS demyelination followed in close time relationship the administration of Gardasil vaccine and we discuss their possible association. http://jnnp.bmj.com/content/82/11/1296.long
Demyelinating disease and vaccination of the human papillomavirus.
We describe the cases of four young women that developed demyelinating disease after the vaccination of the HPV, with a rank of time between the administration of the dose and the development of the clinical of seven days to a month, with similar symptoms with the successive doses. We have described six episodes coinciding after the vaccination. https://www.ncbi.nlm.nih.gov/m/pubmed/21425100/
A dose-response relationship between organic mercury exposure from thimerosal-containing vaccines and neurodevelopmental disorders.
A hypothesis testing case-control study evaluated concerns about the toxic effects of organic-mercury (Hg) exposure from thimerosal-containing (49.55% Hg by weight) vaccines on the risk of neurodevelopmental disorders (NDs). https://www.ncbi.nlm.nih.gov/m/pubmed/25198681/
Encephalitis related to a H1N1 vaccination: case report and review of the literature.
“We report a case of a 26-year-old female who developed symptoms of acute encephalitis 5 days after vaccination against the pandemic 2009 A/H1N1 influenza. MRI of the brain showed confluent T2-hyperintense signal intensity changes in the deep white matter which further confirmed the diagnosis of encephalitis/acute disseminated encephalomyelitis. Despite therapy with immunoglobulins and corticosteroids, her persistent vegetative state continued.” https://www.ncbi.nlm.nih.gov/m/pubmed/24996055/
Encephalomyelitis and bilateral optic perineuritis after influenza vaccination.
We report the case of one patient suffering from headache, urinary retention, bilateral optic disc swelling and a mild bilateral visual defect after influenza vaccination. https://www.ncbi.nlm.nih.gov/m/pubmed/11126677/
Extensive myelitis after oral polio vaccination: MRI features.
A 7-year-old boy presented with fever and ataxia 20 days after oral polio vaccination. https://www.ncbi.nlm.nih.gov/m/pubmed/25786294
Fatal outcome after post exposure rabies vaccination in a patient with Parkinson’s disease.
Parkinson’s disease, with its complications, was the cause of death of the patient bitten by a rabid cat. Furthermore, the coincidence of the progression of Parkinson’s disease symptoms, at the time of post exposure rabies vaccination, points to the vaccine as a possible contributing factor to aggravation of the disease and lethal outcome. https://www.ncbi.nlm.nih.gov/m/pubmed/15675624/
Fetal damage after accidental polio vaccination of an immune mother.
“Irreparable damage to the anterior horn cells of the cervical and thoracic cord was found in a 20-week-old fetus whose mother was immune to poliomyelitis before conceiving but who was inadvertently given oral polio vaccine at 18 weeks gestation. https://www.ncbi.nlm.nih.gov/m/pubmed/6747944/
Guillain-Barré Syndrome after H1N1 Shot in Pregnancy: Maternal and Fetal Care in the Third Trimester-Case Report.
“We presented a case of a 36-year-old pregnant woman that was immunized to H1N1 in the last trimester; 10 days later she developed shoulder and lumbar spine’s pain, limbs weakness and facial paralysis with unfavorable clinical evolution and was submitted to intensive therapy care. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3521405/
Guillain-Barre syndrome after influenza vaccine administration: two adult cases.
“We describe two adult cases of neurologic complications occurring after the administration of the influenza vaccine. The first case described is a 68 year-old man who experienced paresthesias of the upper and lower extremities two weeks after vaccination, and the second case was a 64 year-old female who exhibited paraplegia eighteen days after vaccination. https://www.ncbi.nlm.nih.gov/m/pubmed/20939203/
Guillain-Barré syndrome after vaccination in United States: data from the Centers for Disease Control and Prevention/Food and Drug Administration Vaccine Adverse Event Reporting System (1990-2005).
“There were 1000 cases (mean age, 47 years) of GBS reported after vaccination in the United States between 1990 and 2005. The onset of GBS was within 6 weeks in 774 cases, >6 weeks in 101, and unknown in 125. Death and disability after the event occurred in 32 (3.2%) and 167 (16.7%) subjects, respectively. The highest number (n = 632) of GBS cases was observed in subjects receiving influenza vaccine followed by hepatitis B vaccine (n = 94). Other vaccines or combinations of vaccines were associated with 274 cases of GBS. https://www.ncbi.nlm.nih.gov/m/pubmed/19730016/
Guillain-Barré syndrome among recipients of Menactra meningococcal conjugate vaccine–United States, June-July 2005.
Case 1. A male aged 18 years was vaccinated with MCV4; 15 days later, he experienced tingling in his feet and hands. He had no history of major underlying illness; his mother had had GBS 5 years earlier.
Case 2. A male aged 17 years was vaccinated with MCV4; approximately 25 days later, he had difficulty walking, followed by difficulty moving from a standing to a seated position. Medical history included attention deficit hyperactivity disorder and Asperger syndrome; he had been taking multiple psychotropic medications.
Case 3. A female aged 17 years was vaccinated with MCV4. She had a previous history of GBS at ages 2 and 5 years, both beginning 14 days after vaccination with childhood vaccines.
Case 4. A female aged 18 years was vaccinated with MCV4. Six days after vaccination, she had a sore throat that lasted for 6 days, and 29 days after vaccination she reported a severe headache and was evaluated in an emergency department (ED), where she had a normal computerized tomography (CT) scan, was treated with ketorolac, and discharged on oral ibuprofen.
Case 5. A female aged 18 years was vaccinated with MCV4; 14 days later, she experienced heaviness in her legs when walking upstairs. During the next 8 days, her difficulty walking continued, and she had bilateral leg pain. https://www.cdc.gov/mmwpreview/mmwrhtml/mm5440a6.htm
Guillain – Barre’ syndrome following recombinant hepatitis B vaccine and literature review.
“A 17 year-old woman developed progressive quadriparesis with bilateral facial diplegia after immunization with recombinant hepatitis B vaccine 3 days prior. Cerebrospinal fluid analysis revealed acellular fluid with high protein level. https://www.ncbi.nlm.nih.gov/m/pubmed/11075984/
Guillain-Barre syndrome occurring after rabies vaccination.
“A variety of events are associated with the onset of Guillain-Barre syndrome, including vaccinations and vaccines. These are the swine influenza vaccine, oral poliovirus vaccine and rabies vaccine. Rabies is a uniformly fatal disease. http://jpma.org.pk/full_article_text.php?article_id=601
Gulf war syndrome: could it be triggered by biological warfare-vaccines using pertussis as an adjuvant?
“Several recent epidemiological studies have shown that vaccinations against biological warfare using pertussis as an adjuvant were associated with the Gulf war syndrome. If such epidemiological findings are confirmed, we propose that the use of pertussis as an adjuvant could trigger neurodegeneration through induction of interleukin-1beta secretion in the brain. https://www.ncbi.nlm.nih.gov/m/pubmed/12027522/
Hepatitis B vaccination and associated oral manifestations: a non-systematic review of literature and case reports.
“After reviewing the literature, we observed that complications seen after Hepatitis B vaccination are sudden infant death syndrome, multiple sclerosis, chronic fatigue syndrome, idiopathic thrombocytopenic purpura, vasculititis optic neuritis, anaphylaxis, systemic lupus erytymatosus, lichen planus and neuro-muscular disorder.” https://www.ncbi.nlm.nih.gov/m/pubmed/25506472/
Hypothesis: Human papillomavirus vaccination syndrome–small fiber neuropathy and dysautonomia could be its underlying pathogenesis.
Adverse reactions appear to be more frequent after HPV vaccination when compared to other type of immunizations. Different isolated cases and small series have described the development of complex regional pain syndrome (CRPS), postural orthostatic tachycardia syndrome (POTS), and fibromyalgia after HPV vaccination. https://www.ncbi.nlm.nih.gov/m/pubmed/25990003/
Imported Vaccine-Associated Paralytic Poliomyelitis — United States, 2005
“This report describes the first known occurrence of imported VAPP in an unvaccinated U.S. adult who traveled abroad, where she likely was exposed through contact with an infant recently vaccinated with OPV.”
“Upon admission to a hospital in Phoenix, the patient had bilateral areflexic lower extremity weakness and respiratory failure requiring intubation.” https://www.cdc.gov/mmwpreview/mmwrhtml/mm5504a2.htm
Infant meningoencephalitis caused by yellow fever vaccine virus transmitted via breastmilk.
“In 2009, the first case was confirmed of meningoencephalitis caused by the yellow fever vaccine virus transmitted via breastmilk. We describe a second case in which the vaccine virus was possibly the etiologic agent of meningoencephalitis.” https://www.ncbi.nlm.nih.gov/m/pubmed/21461453/
Influence of pediatric vaccines on amygdala growth and opioid ligand binding in rhesus macaque infants: A pilot study.
“These results suggest that maturational changes in amygdala volume and the binding capacity of [(11)C]DPN in the amygdala was significantly altered in infant macaques receiving the vaccine schedule.” https://www.ncbi.nlm.nih.gov/m/pubmed/20628439/
Influenza vaccine-induced CNS demyelination in a 50-year-old male.
Case reports of CNS demyelination following vaccinations have been previously noted, most often occurring in the context of recent influenza vaccination. https://www.ncbi.nlm.nih.gov/m/pubmed/25175754/
Ischaemic stroke and influenza A H1N1 vaccination: a case report.
“We report a 75-year-old male patient who suffered posterior circulation ischaemia after influenza A/H1N1 vaccination. Vaccination provokes a variable magnitude of inflammatory and immunological response that modifies the risk for ischaemic stroke. Whereas a causal relation between vaccination and ischaemic stroke is still unsettled, an inflammatory/immunological response after vaccination may trigger thrombosis superimposing a pre-existing prothrombotic state. https://www.ncbi.nlm.nih.gov/m/pubmed/22291779/
Lumbosacral acute demyelinating polyneuropathy following hepatitis B vaccination.
“We report a patient who presented with an acute inflammatory demyelinating polyneuropathy, that followed the second injection of a hepatitis B vaccination, and characterized by motor and sensory deficit restricted to lower limbs and perineum, and persistent bladder dysfunction. The relationship between the preceding event and neurological disease is discussed.” https://www.ncbi.nlm.nih.gov/m/pubmed/10520897/
Major Birth Defects after Vaccination Reported to the Vaccine Adverse Event Reporting System (VAERS), 1990 to 2014. (2017)
“We identified 50 reports of major birth defects; in 28 reports, the vaccine was given during the first trimester; 25 were reports with single vaccines administered.” https://www.ncbi.nlm.nih.gov/m/pubmed/28398711/
Measles-mumps-rubella-varicella combination vaccine and the risk of febrile seizures.
‘We alerted the Advisory Committee on Immunization Practices to preliminary evidence of a twofold increased risk of febrile seizures after the combination measles-mumps-rubella-varicella (MMRV) vaccine when compared with separate measles-mumps-rubella (MMR) and varicella vaccines’ https://www.ncbi.nlm.nih.gov/m/pubmed/20587679/
Mental nerve neuropathy as a result of hepatitis B vaccination.
We describe a 20-year-old woman who presented with polyarthralgia and sensory neuropathy, including mental nerve neuropathy. The symptoms were attributed to hepatitis B vaccination. https://www.ncbi.nlm.nih.gov/m/pubmed/9195619/
MRI findings in an infant with vaccine-associated paralytic poliomyelitis.
“We report a Brazilian infant who developed VAPP 40 days after receiving the first dose of oral polio vaccine (OPV). MR images of the cervical and thoracic spinal cord showed lesions involving the anterior horn cell, with increased signal intensity on T2-weighted sequences. https://www.ncbi.nlm.nih.gov/m/pubmed/20440488/
The muscle findings in a pediatric patient with live attenuated oral polio vaccine-related flaccid monoplegia.
A pediatric patient, who was given live-attenuated oral polio vaccine twice without distinct gait disturbance during infancy, begun to present limp at 3 years. His gait disturbance became remarkable with aging. https://www.ncbi.nlm.nih.gov/m/pubmed/25131733/
Neurologic complications due to a sample type of rabies vaccination.
Neuroparalytic accidents due to sample type rabies vaccination are still an important problem in our country. We present seven patients with ascending polyneuritis, due to rabies vaccine, treated between 1982-1986, and discuss the importance of the problem. https://www.ncbi.nlm.nih.gov/m/pubmed/3447020/
Neurologic Complications in HPV Vaccination.
A relatively high incidence of chronic limb pain, frequently complicated by violent, tremulous involuntary movements, has been noted in Japanese girls following human papillomavirus vaccination. https://www.ncbi.nlm.nih.gov/m/pubmed/26160812/
Neurologic complications in oral polio vaccine recipients.
“A vaccine-like strain of poliovirus was isolated from each patient, and each had symptoms (left leg paralysis in three; developmental regression, spasticity, and progressive fatal cerebral atrophy in one) persisting for at least 6 months.” https://www.ncbi.nlm.nih.gov/m/pubmed/3012055/
Neurologic illness following post-exposure prophylaxis with purifiled chick embryo cell antirabies vaccine.
Clinical details of a neurologic illness simultating Guillain Barre syndrome developing in a patient after post-exposure prophylaxis with purified chick embryo cell (PCEC) anti-rabies vaccine is reported. https://www.ncbi.nlm.nih.gov/m/pubmed/11837768/
Neurological and autoimmune disorders after vaccination against pandemic influenza A (H1N1) with a monovalent adjuvanted vaccine: population based cohort study in Stockholm, Sweden.
“Relative risks were significantly increased for Bell’s palsy, paraesthesia, and inflammatory bowel disease after vaccination, predominantly in the early phase of the vaccination campaign.” https://www.ncbi.nlm.nih.gov/m/pubmed/21994316
Neuroparalytic accidents of antirabies vaccination with suckling mouse brain vaccine. Clinical and pathologic study of 21 cases.
“Twenty-one cases of neuroparalytic accidents of rabies vaccination (with suckling mouse brain vaccine), 11 of them fatal, were observed, occurring predominantly in men; the mean age of the patients was 29 years.” https://www.ncbi.nlm.nih.gov/m/pubmed/911231/
Neuropathology of vaccination in infants and children.
Documentation of clinical-pathological features of 37 infants/children whose parents alleged a relationship between vaccination and death or permanent central nervous system (CNS) damage, and sought compensation through the National Vaccine Injury Compensation Program. https://www.ncbi.nlm.nih.gov/m/pubmed/21854821/
The neurotoxicity of environmental aluminum is still an issue
If you think eating aluminum is bad, just think what happens when it’s injected and bypasses the normal protective biological barriers. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2946821/
Nonfebrile seizures after mumps, measles, rubella, and varicella-zoster virus combination vaccination with detection of measles virus RNA in serum, throat, and urine.
“We report the case of a child presenting with nonfebrile seizures 6 and 13 days after the first vaccination with a measles, mumps, rubella, and varicella (MMRV) combination vaccine. Measles virus RNA was detected in the patient’s serum, throat, and urine. Genotyping revealed the Schwarz vaccine virus strain.” https://www.ncbi.nlm.nih.gov/m/pubmed/23637042/
A novel vaccinological evaluation of intranasal vaccine and adjuvant safety for preclinical tests.
“However, the addition of adjuvants to vaccines may cause unwanted immune responses, including facial nerve paralysis and narcolepsy. ” https://www.ncbi.nlm.nih.gov/m/pubmed/28063707/
Opsoclonus Myoclonus after human papilloma virus vaccine in a pediatric patient.
“Opsoclonus-Myoclonus Syndrome (OMS) is a rare neurologic condition comprised of the two hallmark signs of dysmetric ocular ataxia and myoclonic jerks of the extremities. The patient was a fully vaccinated and developmentally appropriate 11-year-old female with seasonal allergies and mild asthma. Her initial symptoms consisted of a sudden onset of increased “moodiness” causing uncharacteristic anger and depression. These symptoms presented approximately 15 days after receiving her first human papilloma virus (HPV) (Gardisil®) vaccination on 11/26/2007. https://www.ncbi.nlm.nih.gov/m/pubmed/19447066/
Partial third nerve palsy after MMR.
Measles Mumps Rubella (MMR) vaccination is known to cause some serious adverse events, such as fever, rash, gland inflammation and neurologic disorders. These include third and sixth cranial nerve palsies. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2944153/
Peripheral sympathetic nerve dysfunction in adolescent Japanese girls following immunization with the human papillomavirus vaccine.
During the past nine months, 44 girls visited us complaining of several symptoms after HPV vaccination. Four patients with other proven disorders were excluded, and the remaining forty subjects were enrolled in this study. https://www.ncbi.nlm.nih.gov/m/pubmed/25274229/
A possible central mechanism in autism spectrum disorders, part 1.
“The autism spectrum disorders (ASD) are a group of related neurodevelopmental disorders that have been increasing in incidence since the 1980s. A careful review of ASD cases discloses a number of events that adhere to an immune-excitotoxic mechanism. This mechanism explains the link between excessive vaccination, use of aluminum and ethylmercury as vaccine adjuvants, food allergies, gut dysbiosis, and abnormal formation of the developing brain. http://www.ncbi.nlm.nih.gov/pubmed/19043938
Postpartum rubella immunization: association with development of prolonged arthritis, neurological sequelae, and chronic rubella viremia.
Six women developed chronic long-term arthropathy after postpartum immunization against rubella. All individuals developed acute polyarticular arthritis within 12 days to three weeks postimmunization and have had continuing chronic or recurrent arthralgia or arthritis for two to seven years after vaccination. https://www.ncbi.nlm.nih.gov/m/pubmed/4031558/
Postvaccinal complication and medical malpractice law.
“The case report involves a 38-year-old female patient with muscular atrophy, paresis and sensory deficits in the right upper limb following several vaccinations. A legal dispute ensued over whether medical malpractice could have caused the neurological deficits. Medical malpractice could not be confirmed. Even vaccinations administered correctly can lead to neurological impairment.” https://www.ncbi.nlm.nih.gov/m/pubmed/27483686/
Post-vaccination encephalomyelitis: literature review and illustrative case.
Post-vaccination ADEM has been associated with several vaccines such as rabies, diphtheria-tetanus-polio, smallpox, measles, mumps, rubella, Japanese B encephalitis, pertussis, influenza, hepatitis B, and the Hog vaccine. We review ADEM with particular emphasis on vaccination as the precipitating factor. https://www.ncbi.nlm.nih.gov/m/pubmed/18976924/
Postvaccinal parkinsonism.
A 5-year-old boy, with a history of fever beginning 15 days after a vaccination for measles, developed a rigid-akinetic syndrome 3 days after the fever began. A spinal tap obtained 1 week after the onset of fever showed pleocytosis with a monocellular pattern. https://www.ncbi.nlm.nih.gov/m/pubmed/1350062/
Prolonged exposure to low levels of aluminum leads to changes associated with brain aging and neurodegeneration
“Epidemiological studies suggest that aluminum may not be as innocuous as was previously thought and that aluminum may actively promote the onset and progression of Alzheimer’s disease.” https://www.ncbi.nlm.nih.gov/m/pubmed/24189189/
Recurrent encephalitis following annual influenza vaccine. Case report.
“We report the case of a male patient that presented two episodes of acute encephalitis in consecutive years, 16 and 20 days after his annual influenza vaccine shot, respectively. In both instances, patient required ICU admission and evolved with fast recovery and no sequels.” https://www.ncbi.nlm.nih.gov/m/pubmed/27315001/

Acute flaccid paralysis surveillance indicators in the Democratic Republic of Congo during 2008-2014
“Of the 13,749 AFP cases investigated, 58.9% received at least three doses of oral polio vaccine (OPV), 7.3% never received OPV, while the status of 18.3% was unknown.” Pan African Medical Journal 2016 https://www.ncbi.nlm.nih.gov/m/pubmed/27642491
Adverse events associated with childhood vaccines other than pertussis and rubella. Summary of a report from the Institute of Medicine.
The committee found that the evidence favored acceptance of a causal relation between diphtheria and tetanus toxoids and Guillain-Barré syndrome and brachial neuritis, between measles vaccine and anaphylaxis, between oral polio vaccine and Guillain-Barré syndrome, and between unconjugated Hib vaccine and susceptibility to Hib disease. The committee found that the evidence established causality between diphtheria and tetanus toxoids and anaphylaxis, between measles vaccine and death from measles vaccine-strain viral infection, between measles-mumps-rubella vaccine and thrombocytopenia and anaphylaxis, between oral polio vaccine and poliomyelitis and death from polio vaccine-strain viral infection, and between hepatitis B vaccine and anaphylaxis. JAMA 1994 https://www.ncbi.nlm.nih.gov/m/pubmed/8182813/
‘An American tragedy’. the Cutter incident and its implications for the Salk polio vaccine in New Zealand 1955-1960.
“During the United States polio immunisation campaign in 1955 a number of children immunised with Cutter Laboratories vaccine were stricken with the disease, halting the programme.” Health History 1990 https://www.ncbi.nlm.nih.gov/m/pubmed/20481116/
Aseptic meningitis after vaccination against measles and mumps
“This retrospective study (1979 to 1986) investigated the possible etiologic relationship between vaccination and aseptic meningitis in 115 hospitalized children who became ill within 30 days of vaccination with the Leningrad 3 strain of mumps virus and the Edmonston-Zagreb strain of measles virus.” The Pediatric Infectious Disease Journal 1989 https://www.ncbi.nlm.nih.gov/m/pubmed/2726323/
Bordetella parapertussis outbreak in Southeastern Minnesota and the United States, 2014. (2017)
“All patients were vaccinated against pertussis, suggesting that pertussis vaccination is ineffective against B. parapertussis.” Medicine 2017 https://www.ncbi.nlm.nih.gov/m/pubmed/28514288/
Canine rabies in Nigeria, 1970 – 1980 reported cases in vaccinated dogs.
“Of the 14 cases there were 10 cases of apparent vaccine failure involving modified live (low egg passage chick embryo) vaccine in use during the study period. In 4 of these cases, infection may actually have been induced by the vaccine.” International Journal of Zoonoses 1982 https://www.ncbi.nlm.nih.gov/m/pubmed/7169305
CASE OF VACCINE-ASSOCIATED MEASLES FIVE WEEKS POST-IMMUNISATION
http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20649
Challenges in Interpretation of Diagnostic Test Results in a Mumps Outbreak in a Highly Vaccinated Population. 2017
“This is the first published report of an outbreak of mumps in Ontario in which all confirmed cases had been vaccinated against the disease.” Clinical and Vaccine Immunology 2017 https://www.ncbi.nlm.nih.gov/m/pubmed/28003216/
Characteristics of poliovirus strains from long-term excretors with primary immunodeficiencies.
“ Long-term excretion of vaccine strains of poliovirus has been documented for many years and instances of paralytic poliomyelitis in hypogammaglobulinaemic patients who were subsequently found to have been excreting virus for prolonged periods have been reported in the U.S.A., Germany and Japan.” Developmental Biology 2001 https://www.ncbi.nlm.nih.gov/m/pubmed/11763340
Chronic progressive poliomyelitis secondary to vaccination of an immunodeficient child.
“We investigated an immunodeficient child in whom chronic progressive poliomyelitis developed after she had received live oral poliovirus vaccine. Poliovirus, Type II, was isolated from throat and stool during life and from several sites within the brain at autopsy.” The New England Journal of Medicine 1977 https://www.ncbi.nlm.nih.gov/m/pubmed/195206
Comparison of neutralizing antibody titers against outbreak-associated measles genotypes (D4, H1 and B3) in Iran.
“Despite the accessibility of a promising vaccine, outbreaks of the measles virus (MV) take place even in well-vaccinated populations.” Pathogens and Disease 2016 https://www.ncbi.nlm.nih.gov/m/pubmed/27777263/
Continuing measles transmission in students despite school-based outbreak control program.
“Forty-six cases occurred among students more than two weeks after control program implementation. All 46 had a school record indicating adequate measles vaccination; 13 had been vaccinated at control program clinics by one jet-injector team (Team A).” American Journal of Epidemiology 1985 https://www.ncbi.nlm.nih.gov/m/pubmed/4014205/
Deep sequencing reveals persistence of cell-associated mumps vaccine virus in chronic encephalitis.
“Notwithstanding this, we describe here devastating neurological complications associated with the detection of live-attenuated mumps virus Jeryl Lynn (MuV(JL5)) in the brain of a child who had undergone successful allogeneic transplantation for severe combined immunodeficiency (SCID). This is the first confirmed report of MuV(JL5) associated with chronic encephalitis and highlights the need to exclude immunodeficient individuals from immunisation with live-attenuated vaccines.” Acta Neuropathologica 2017 https://www.ncbi.nlm.nih.gov/m/pubmed/27770235/
Detection of fecal shedding of rotavirus vaccine in infants following their first dose of pentavalent rotavirus vaccine.
“Studies on rotavirus vaccine shedding and its potential transmission within households including immunocompromised individuals are needed to better define the potential risks and benefits of vaccination.” Vaccine 2011 https://www.ncbi.nlm.nih.gov/m/pubmed/21477676/
Disseminated, persistent, and fatal infection due to the vaccine strain of varicella-zoster virus in an adult following stem cell transplantation.
“Here, we describe the fatality of an immunocompromised patient who received the varicella vaccine. His medical history provides a cautionary lens through which to view the decision of when vaccination is appropriate. A middle-aged man with non-Hodgkin lymphoma received chemotherapy and a stem cell transplant. He was vaccinated 4 years post-transplantation, despite diagnosis of a new low-grade lymphoma confined to the lymph nodes.” Clinical Infectious Diseases 2016 https://www.ncbi.nlm.nih.gov/m/pubmed/25452596
Efficacy of a Russian-backbone live attenuated influenza vaccine among children in Senegal: a randomised, double-blind, placebo-controlled trial.
“INTERPRETATION: Live attenuated influenza vaccine was well tolerated in young children in Senegal, but did not provide protection against influenza.” The Lancet Global Health 2016 https://www.ncbi.nlm.nih.gov/m/pubmed/27746224/
An emergent poxvirus from humans and cattle in Rio de Janeiro State: Cantagalo virus may derive from Brazilian smallpox vaccine.
“Together, the data suggested that CTGV may have derived from VV-IOC by persisting in an indigenous animal(s), accumulating polymorphisms, and now emerging in cattle and milkers as CTGV. CTGV may represent the first case of long-term persistence of vaccinia in the New World. Virology 2000 https://www.ncbi.nlm.nih.gov/m/pubmed/11080491/
Evidence for immunisation failure in vaccinated adult dogs infected with canine parvovirus type 2c
“An outbreak of canine parvovirus type 2c (CPV-2c) infection in vaccinated adult dogs is reported.” New Microbiologica 2008 https://www.ncbi.nlm.nih.gov/m/pubmed/18437851
Explosive school-based measles outbreak: intense exposure may have resulted in high risk, even among revaccinees.
“The authors studied inoculum intensities as measured by proxy variables and the contagiousness of properly vaccinated persons who contracted measles among 51 measles patients infected in one school, at home, or elsewhere, utilizing preexisting records of measles cases and 214 healthy controls from an explosive school outbreak that occurred in a rural Finnish municipality in 1989.” American Journal of Epidemiology 1998 https://www.ncbi.nlm.nih.gov/m/pubmed/9850133/
Failed rubella immunization in adults: association with immunologic and virological abnormalities.
“Immunologic and virological studies were performed in 13 adults (12 women and one man) who failed to seroconvert (as shown by rubella hemagglutination-inhibition [HAI] techniques) after single or repeated courses of HPV-77 DE/5 or RA 27/3 rubella virus vaccine.” The Journal of Infectious Diseases 1985 https://www.ncbi.nlm.nih.gov/m/pubmed/3968452/
The failure of an inactivated mink enteritis virus vaccine in four preparations to provide protection to dogs against challenge with canine parvovirus-2
“Four experimental vaccine preparations comprising a strain of mink enteritis virus inactivated by either formalin or beta-propiolactone, and either adjuvanted or nonadjuvanted, failed to stimulate a consistent serum antibody response in 20 vaccinated dogs and failed to protect all but one of these dogs against oral challenge with canine parvovirus-2.” Canadian Journal of Comparative Medicine 1982 https://www.ncbi.nlm.nih.gov/m/pubmed/6280820
Failure of inactivated influenza A vaccine to protect healthy children aged 6-24 months.
“Inactivated influenza vaccine did not reduce the attack rate of influenza A infection in 6-24 month old children.” Pediatrics International 2004 https://www.ncbi.nlm.nih.gov/m/pubmed/15056235
Failure to reach the goal of measles elimination. Apparent paradox of measles infections in immunized persons.
“RESULTS: We found 18 reports of measles outbreaks in very highly immunized school populations where 71% to 99.8% of students were immunized against measles.” Archives of Internal Medicine 1994 https://www.ncbi.nlm.nih.gov/m/pubmed/8053748/?i=6
Fever and multisystem organ failure associated with 17D-204 yellow fever vaccination: a report of four cases.
“FINDINGS: The clinical presentations were characterised by fever, myalgia, headache, and confusion, followed by severe multisystemic illnesses. Three patients died. Vaccine-related variants of yellow fever virus were found in plasma and cerebrospinal fluid of one vaccinee. The convalescent serum samples of two vaccinees showed antibody responses of at least 1:10240. Immunohistochemical assay of liver tissue showed yellow fever antigen in the Kuppfer cells of the liver sample.” Lancet 2001 https://www.ncbi.nlm.nih.gov/m/pubmed/11463410/
Finding the ‘who’ in whooping cough: vaccinated siblings are important pertussis sources in infants 6 months of age and under.
“At its peak, siblings were the most important sources of pertussis in infants 6 months and younger, particularly fully vaccinated children aged 2 and 3 years. Waning immunity before the booster at 4 years may leave this age group susceptible to infection.” Communicable Diseases Intelligence Quarterly Report 2014 https://www.ncbi.nlm.nih.gov/m/pubmed/25391405/
Haemophilus influenzae type b meningitis in a vaccinated and immunocompetent child.
“We report a case of a fifteen-months-old girl, previously healthy and vaccinated, admitted in the emergency room with fever and vomiting. She was irritable and the Brudzinski’s sign was positive.” Journal of Infection and Public Health 2017 https://www.ncbi.nlm.nih.gov/m/pubmed/27422142
Haemophilus influenzae Type b Meningitis in the Short Period after Vaccination: A Reminder of the Phenomenon of Apparent Vaccine Failure.
“We present two cases of bacterial meningitis caused by Haemophilus influenzae type b (Hib) which developed a few days after conjugate Hib vaccination. This phenomenon of postimmunization provocative time period is reviewed and discussed. These cases serve as a reminder to clinicians of the risk, albeit rare, of invasive Hib disease in the short period after successful immunization.” Case Reports in Infectious Diseases 2012 https://www.ncbi.nlm.nih.gov/m/pubmed/22953084/
Hepatitis B Vaccines—to Switch or Not to Switch
“Shortly after the licensure of Heptavax-B in 1981 and its general availability in July 1982, the discovery of the acquired immunodeficiency syndrome (AIDS) among male homosexuals threatened the success of this product, since some of the hepatitis B surface antigen (HBsAg)-positive plasma donors were members of this high-risk group. Intensive epidemiologic, virological, and serological evaluations were launched, which eventually found no evidence for the transmission of AIDS to recipients of the plasma-derived HBsAg vaccine.” JAMA 1987 http://jamanetwork.com/journals/jama/article-abstract/366144
Herpes zoster due to Oka vaccine strain of varicella zoster virus in an immunosuppressed child post cord blood transplant.
“A 5-year-old boy was vaccinated with the Oka strain of varicella zoster virus vaccine before cord blood transplant for chronic granulomatous disease in 2005. In 2006, he developed herpes zoster on his left arm. DNA from the vesicular rash confirmed the Oka vaccine strain of varicella zoster virus caused this complication. He responded well to 10 days of aciclovir treatment.” Journal of Paediatrics and Child Health 2007 https://www.ncbi.nlm.nih.gov/m/pubmed/17854459
Herpes zoster in an adult recipient of live attenuated varicella vaccine.
“A healthy 30-y-old female physician who was immunized with two doses of live attenuated varicella vaccine developed a localized case of zoster involving the right T8-10 dermatomes 36 mo after vaccination. The virus isolated from her rash was an unusual wild-type of varicella-zoster virus. After immunization she developed detectable antibodies to varicella-zoster virus, but antibodies were no longer detectable after 20 mo.” The Journal of Infectious Diseases 1989 https://www.ncbi.nlm.nih.gov/m/pubmed/2547882
High diversity of poliovirus strains isolated from the central nervous system from patients with vaccine-associated paralytic poliomyelitis.
“To establish the etiology of vaccine-associated paralytic poliomyelitis (VAPP), isolates from the central nervous system (CNS) from eight patients with VAPP were compared with stool isolates from the same patients.” Journal of Virology 1994 https://www.ncbi.nlm.nih.gov/m/pubmed/7966599/
High rate of vaccine failure after administration of acellular pertussis vaccine pre- and post-liver transplantation in children at a children’s hospital in Japan.
“We assessed the serological response to pertussis vaccines administered pre- and post-liver transplantation in 58 pediatric patients at a children’s hospital in Japan.” Transplant Infectious Disease 2016 https://www.ncbi.nlm.nih.gov/m/pubmed/26565897
Horizontal transmission of a human rotavirus vaccine strain–a randomized, placebo-controlled study in twins
“Transmission of excreted vaccine-derived infectious virus from vaccinated to unvaccinated individuals is possible within close contacts.” Vaccine 2011 https://www.ncbi.nlm.nih.gov/m/pubmed/22008819/
Horizontal transmission of the Leningrad-Zagreb mumps vaccine strain: a report of six symptomatic cases of parotitis and one case of meningitis.
“Here we report horizontal symptomatic transmission of the Leningrad-Zagreb (L-Zagreb) mumps vaccine virus. Children who were the source of transmission had been vaccinated with the MMR vaccine (Serum Institute of India) contained L-Zagreb mumps virus. This is the first report of horizontal symptomatic transmission of this vaccine. The etiology of all seven contact cases was confirmed by epidemiological linking, serology and by F, SH, NP and HN mumps virus genes sequencing.” Vaccine 2012 https://www.ncbi.nlm.nih.gov/m/pubmed/22749598/
Immune persistence after pertussis vaccination.
“An increased prevalence of pertussis in older populations has been found, mainly caused by waning immunity after vaccination.” Human Vaccines & Immunotherapeutics 2017 https://www.ncbi.nlm.nih.gov/m/pubmed/28045580
Interference of Vaccine Derived Polio Viruses with Diagnosis of Enteroviral Diseases in Neonatal Period.
“OPV vaccinated neonates commonly pass the vaccine virus in their pharynx and stool which can be mistaken with NPEV.” Journal of Clinical and Diagnostic Research 2016 https://www.ncbi.nlm.nih.gov/m/pubmed/28050469
Invasive pneumococcal disease: From a tertiary care hospital in the post-vaccine era
“A breakthrough infection occurring with 13-valent pneumococcal conjugate vaccine (PCV13) in Turkey are previously described.” Human Vaccines & Immunotherapeutics 2017 https://www.ncbi.nlm.nih.gov/m/pubmed/27905836/
A large vaccine-derived poliovirus outbreak on Madura Island–Indonesia, 2005.
“Between June and October 2005, 45 laboratory-confirmed type 1 vaccine-derived poliovirus (VDPV) cases were identified on Madura Island in Indonesia. Genetic sequencing data on VDPV isolates were consistent with replication and circulation for up to approximately 2 years. Concurrent circulation with type 1 wild poliovirus (WPV) enabled comparisons of VDPV and WPV cases and found that clinical and epidemiological features of both were similar. Attack rates for VDPV were as high as those for WPV. Of 41 VDPV case patients with known vaccination status, 25 (61%) had received zero oral polio vaccine (OPV) doses.” The Journal of Infectious Diseases 2008 https://www.ncbi.nlm.nih.gov/m/pubmed/18199031/
Late vitamin K deficiency bleeding after intramuscular prophylaxis at birth: a case report
“We report the case of a 6-week-old female who presented an intracranial hemorrhage due to late vitamin K deficiency bleeding (VKDB).” Journal of Perinatology 2009 https://www.ncbi.nlm.nih.gov/m/pubmed/19177046
LESSONS FROM THE SALK POLIO VACCINE: METHODS FOR AND RISKS OF RAPID TRANSLATION
“Regretfully, the story of polio vaccine was not without tragedy. In April 1955, soon after mass polio vaccination began in the United States, reports trickled in to the Surgeon General concerning atypical cases of paralytic polio. Several paralytic polio cases were reported in California in patients who had received the polio vaccine about a week earlier but the paralysis only affected the arm or leg in which they received the injection. Each of these cases occurred in polio vaccine produced by Cutter pharmaceutical company. The Surgeon General immediately pulled all Cutter polio vaccine, but it was too late; nearly 400,000 children had been inoculated with Cutter polio vaccine and 250 cases of atypical paralytic polio occurred. There were also reports of the Wyeth pharmaceutical company polio vaccine causing paralysis and death in several children in the northeastern United States.” Clinical and Translational Science 2010 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2928990/
Live attenuated varicella vaccine: evidence that the virus is attenuated and the importance of skin lesions in transmission of varicella-zoster virus. National Institute of Allergy and Infectious Diseases Varicella Vaccine Collaborative Study Group.
“To examine whether the live varicella vaccine virus is attenuated, we analyzed varicella vaccine-induced contact cases of clinical chickenpox in healthy siblings of immunized children with leukemia. A rash developed approximately 1 month later in 156 children with leukemia who had been vaccinated. Vaccine-type virus was isolated from 25 of these children.” Journal of Pediatrics 1990 https://www.ncbi.nlm.nih.gov/m/pubmed/2153790/
Local public health response to vaccine-associated measles: case report.
“A five-year-old Canadian-born boy with a history of a hematopoetic stem cell transplant three years previously received live attenuated measles, mumps, and rubella (MMR) vaccine. Over the subsequent 7 to 14 days, he developed an illness clinically consistent with measles. There was no travel history or other measles exposure. Serology and polymerase chain reaction (PCR) testing confirmed acute measles infection.” BMC Public Health 2013 https://www.ncbi.nlm.nih.gov/m/pubmed/23531102/
Low vaccine efficacy of mumps component among MMR vaccine recipients in Chennai, India
“These facts inevitably state that MMR vaccine failed to offer protection in vaccinated individuals against mumps infection.” Indian Journal of Medical Research 2014 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4140044/
A limited measles outbreak in a highly vaccinated US boarding school
“OBJECTIVES: We investigated a measles outbreak that began in March 2003 in a Pennsylvania boarding school with >600 students to identify all cases, including the source; implement outbreak control measures; and evaluate vaccine effectiveness.” Pediatrics 2005 https://www.ncbi.nlm.nih.gov/m/pubmed/16322148
Live, attenuated varicella zoster vaccination of an immunocompromised patient.
“ vaccine for the prevention of herpes zoster outbreaks in adults over the age of 60 years has recently been approved. A 76-year-old white female with a history of recurrent left axillary breast cancer undergoing chemotherapy was given a Zostavax injection by her primary care physician.” Journal of General Internal Medicine 2008 https://www.ncbi.nlm.nih.gov/m/pubmed/18286341
Major measles epidemic in the region of Quebec despite a 99% vaccine coverage
“Vaccination coverage for the total population was 99.0%. Incomplete vaccination coverage is not a valid explanation for the Quebec City measles outbreak.” Journal Public Health 1991 https://www.ncbi.nlm.nih.gov/m/pubmed/1884314/
Measles outbreak in a fully immunized secondary-school population.
“An outbreak of measles occurred among adolescents in Corpus Christi, Texas, in the spring of 1985, even though vaccination requirements for school attendance had been thoroughly enforced.” The New England Journal of Medicine 1987 https://www.ncbi.nlm.nih.gov/m/pubmed/3821823/
A measles outbreak in a middle school with high vaccination coverage and evidence of prior immunity among cases, Beijing, P.R. China.
“CONCLUSIONS: This is the first report from China showing measles transmission among persons with prior evidence of immunity.” Vaccine 2017 https://www.ncbi.nlm.nih.gov/m/pubmed/26589518
Mechanism of Injury-Provoked Poliomyelitis
“Skeletal muscle injury is known to predispose its sufferers to neurological complications of concurrent poliovirus infections. This phenomenon, labeled “provocation poliomyelitis,” continues to cause numerous cases of childhood paralysis due to the administration of unnecessary injections to children in areas where poliovirus is endemic.” Journal of Virology 1998 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC110068/
Modified chickenpox in children immunized with the Oka/Merck varicella vaccine.
“The severity of chickenpox in healthy children who have received Oka/Merck varicella vaccine since 1981 is described.” Pediatrics 1993 https://www.ncbi.nlm.nih.gov/m/pubmed/8416499/
Molecular typing of canine parvovirus strains circulating from 2008 to 2012 in an organized kennel in India reveals the possibility of vaccination failure
“The CPV {Canine parvovirus} vaccines used in the present study failed to generate protective antibody titer against heterogeneous CPV antigenic types. The findings were confirmed when the affected pups were treated with hyper-immune heterogeneous purified immunoglobulin’s against CPV in dogs of different antigenic types. Infection, Genetics and Evolution 2014 https://www.ncbi.nlm.nih.gov/m/pubmed/24486948
MRI findings in an infant with vaccine-associated paralytic poliomyelitis.
“We report a Brazilian infant who developed VAPP 40 days after receiving the first dose of oral polio vaccine (OPV). MR images of the cervical and thoracic spinal cord showed lesions involving the anterior horn cell, with increased signal intensity on T2-weighted sequences. We would like to emphasize the importance of considering VAPP as a differential diagnosis in patients with acute flaccid paralysis and an MRI showing involvement of medulla oblongata or spinal cord, particularly in countries where OPV is extensively administered.” Pediatric Radiology 2010 https://www.ncbi.nlm.nih.gov/m/pubmed/20440488/
Mumps epidemic in vaccinated children in West Switzerland
“Since 1991, 6 years after the recommendation of universal childhood vaccination against measles, mumps, and rubella (MMR triple vaccine), Switzerland is confronted with a large number of mumps cases affecting both vaccinated and unvaccinated children. Up to 80% of the children suffering from mumps between 1991 and 1995 had previously been vaccinated, the majority with the Rubini vaccine strain.” Schweizerische Medizinische Wochenschrift 1997 https://www.ncbi.nlm.nih.gov/m/pubmed/9312835/
Mumps vaccine virus transmission
“In this work we report the mumps vaccine virus shedding based on the laboratory confirmed cases of the mumps virus (MuV) infection. The likely epidemiological sources of the transmitted mumps virus were children who were recently vaccinated with the mumps vaccine containing Leningrad-Zagreb or Leningrad-3 MuV. The etiology of the described cases of the horizontal transmission of both mumps vaccine viruses was confirmed by PCR with the sequential restriction analysis.” Voprosy Virusologii 2013 https://www.ncbi.nlm.nih.gov/m/pubmed/24772647/
Neonatal paralytic poliomyelitis. A case report.
“We report a child who became symptomatic with apnea at 18 days of age and who subsequently developed a permanent monoparesis. Serologic and cultural evidence indicated the virus as poliovirus vaccine type. Another infant who received live oral poliovirus vaccine was probably the source of the infecting virus.” Archives of Neurology 1986 https://www.ncbi.nlm.nih.gov/m/pubmed/3947264/
Neurologic complications in oral polio vaccine recipients.
“A vaccine-like strain of poliovirus was isolated from each patient, and each had symptoms (left leg paralysis in three; developmental regression, spasticity, and progressive fatal cerebral atrophy in one) persisting for at least 6 months.” Journal of Pediatrics 1986 https://www.ncbi.nlm.nih.gov/m/pubmed/3012055/
Outbreak of aseptic meningitis associated with mass vaccination with a urabe-containing measles-mumps-rubella vaccine: implications for immunization programs.
“A mass immunization campaign with a Urabe-containing measles-mumps-rubella vaccine was carried out in 1997 in the city of Salvador, northeastern Brazil, with a target population of children aged 1-11 years. There was an outbreak of aseptic meningitis following the mass campaign.” American Journal of Epidemiology 2000 https://www.ncbi.nlm.nih.gov/m/pubmed/10707922/