Again, tetanus toxoid comes in a variety of vaccine formulations and to prevent tetanus we really must pay attention to wound care. Cleaning the wound, making sure you debride any devitalized tissue and taking out any foreign body.
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Finally, you put the D and T together with a pertussis component and you get DTaP vaccine, the acellular pertussis component, and that includes various components of Bordetella pertussis. Including possibly pertussis toxin, filamentous hemagglutinin, pertactin (pertucin?) fimbriae and a variety of combinations of these which we will get to. The main difference with DTaP vaccine and whole cell DTP vaccine is the decreased endotoxin content in the acellular formulation. This is given in a five day series, two for six months, 12-18 months and finally at 4-6 years of age. You do not give pertussis vaccines, at this point, at seven years of age and older. Only less than seven years of age. The efficacy of the DTaP vaccine is similar to DTP vaccine. About 80-95% and the reaction is lower rate to the common reactions compared to the DTP vaccine. Mostly because of the decreased endotoxin content. The DTaP vaccines are shown in this slide. These are all the FDA-approved vaccines. They are all different. They have different names, different manufacturers and different compositions; a variety of different antigens that are produced in different ways, they are in the vaccine in different quantities. For purposes of taking the test, these are all similar in terms of reactagenicity. There is no meaningful clinical differences between the reactagenicity and there are no meaningful differences between the efficacies of these vaccines and immunogenicities of these vaccines for test taking purposes. There is no difference in efficacy. So you really don’t have to spend too much time on the names and all that. But you do need to know that they are all different and they have different composition. The FDA has approved these for different doses. Really, from a practical standpoint, you can use any of these vaccines at any time. And these vaccines are interchangeable, although it is preferable for at least the first three doses to use the same vaccine, but not required.
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The relative contraindications to pertussis vaccine are shown in this slide and this is different from an absolute contraindication. Pertussis, as you know, can be a very severe disease. So depending on a risk of a subject to pertussis and the complications that they could get from the disease, you need to weigh the risks and benefits. But prior vaccine reaction is a relative contraindication. That’s encephalopathy within seven days, a seizure within three days, persistent crying for three or more hours, collapse state or hypotonic hypo-responsive episode, fever greater than or equal to 40.5 C or an anaphylactic reaction. These are relative contraindications to further vaccination with any pertussis component vaccine. Anybody with a known or suspected progressive neurologic disorder or recent seizures. If you give the vaccine it may result in fever. Fever lowers the seizure threshold, this may induce the seizure and it may confuse the clinical picture. So anybody with those conditions or a known or suspected neurologic condition that predisposes to seizures or neurologic deterioration – the common example of that is tuberous sclerosis, where somebody may have tuberous sclerosis and may not show any signs or symptoms but you know that they are at risk for developing them – giving the vaccine may result in lowering the seizure threshold and then you are not sure. Was it the vaccine? Was it the disease? So you need to think about that.
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In terms of specific vaccines, and we’ll talk about these when indicated, there are hyperimmune globulins with higher titer of antibody.These preparations are for hepatitis B, V-fig, tetanus immune globulin, rabies immune globulin and I hope we’ll have time to talk about RSV as well and the specific indications for that. Now we are going to talk about the specific vaccines, and also sometimes we will talk about the specific diseases if they haven’t been covered elsewhere in the course. This is a slide from the CDC showing tonsillar diphtheria and diphtheria is produced, a toxin-mediated disease, by Carinii bacterium diphtheria. This normally causes a respiratory disease. You can get cutaneous diphtheria also, and at other sites. The complication comes from the toxin which is a toxin that may cause myocarditis and other complications. Diphtheria vaccine is a toxoid vaccine, so it is taking the toxin and inactivating it. Therefore vaccination will not prevent colonization but it will prevent disease. There are two vaccine formulations. There is a big D, and you will see that with the DTaP, DTPM and DT vaccines, and then the little d, the TD vaccine and that’s to be used seven years of age and older. A smaller dose of the diphtheria toxoid and that’s all that’s needed for booster doses. When we talk about HIB vaccines you’ll notice some of them use, as a carrier, diphtheria toxoid. Diphtheria toxoid as a carrier in the HIB vaccine is not a primary immunogen and you can’t count that as vaccinating against diphtheria. You have to have the big D or the little d to count it as a diphtheria immunization.
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Next we’ll talk about tetanus. This is a slide also from the CDC which shows a subject with opisthotonos, which is muscle spasm from tetanus. This is a neurotoxin and in pediatrics, one of the main problems with tetanus is neonatal tetanus. And this child has neonatal tetanus. This slide is from the WHO and this shows this child with this sardonic smile of neonatal tetanus. This is lockjaw in a baby and this occurs in areas of the world where the mothers are not immune to tetanus. So their children are born without the passively acquired tetanus antibodies. Commonly the umbilical stump, which is devitalized tissue, may get infected with Clostridium tetani which is an anaerobe, and then it produces the toxin and causes – it’s a neurotoxin – and causes lockjaw, muscle spasm. So to prevent term tetanus we have two tools available to us; active immunization and passive immunization. Tetanus toxoid, again toxin-mediated disease, purified component will prevent disease. Will not prevent colonization. Vaccine formulations include DTaP, DTP, DT and TD and tetanus immune globulin may also be used. That’s a hyperimmune globulin against tetanus, with high titers of tetanus antibodies. Then the issue comes up, when do you use the toxoid, when do you use tetanus immune globulin? The thing to remember about tetanus is that it is ubiquitous in the environment. It’s in dirt and it’s all around and because of that when a wound occurs, if the wound is contaminated and there is any sort of anaerobic tissue, devitalized tissue or foreign body, this may result in the organism colonizing the wound, producing the neurotoxin and then somebody coming down with tetanus. So if somebody has a wound that is significant and they’ve had less than three tetanus immunizations, then they need to be immunized and given tetanus immune globulin for a dirty wound only; three or more past tetanus immunizations, for dirty wounds immunized just more than five years since the last dose; and for clean wounds, immunized if more than ten years for the last dose. But in any case, if they’ve had three or more past tetanus immunizations you don’t need to give tetanus immune globulin because when you give tetanus toxoid there is a rapid memory response, an anamnestic response, that does result in adequate antibody to make sure that even if the organism is there that there will be enough antibody to fight off the toxin and prevent the disease.
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The question arises; what’s a dirty wound, what’s a clean wound? All I can do is really give you an example. A patient is riding their motorcycle through a cow pasture, they crash into a rusty barbed wire fence, they have a mangled leg, devitalized tissue and they have some cow dung in the wound. That’s a dirty wound. A clean wound is, you are at home, you are slicing tomatoes and you make a nice clean slice in your finger and that’s a clean wound. You can wash it out, there is no foreign bodies in there, there is no real devitalized tissue, you can approximate the edges nicely. That will heal over nicely, and that’s a clean wound. So it’s a question of contamination and risk of disease from the wound.
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So here we go to the heart of the matter, and this is the routine vaccination schedule for children in this country. And this is from the MMWR published by the CDC and this is approved by the American Academy of Pediatrics, the American Academy of Family Practice, and this is really just the general immunization schedule, that if you know this, you will know almost everything there is to know about immunization and for the next hour. So that’s all you have to memorize is this. For hepatitis B, in general, the shots – and we’ll talk about some of the recent changes in that. DTaP vaccine, five dose series; H. flu type B vaccine is three or four doses; for polio that has been a little bit changed but in general it’s four doses, and the first two are ITV. Rotavirus we will skip. MMR vaccine a two dose series; and varicella, one dose of varicella vaccine in general on the routine schedule. So this is all pretty straightforward and everything is pretty easy, right?
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So the other part of this table is that there are just a few little footnotes and so this does tend to get a little bit complicated and that’s in regards to the individual vaccines. So we are going to talk about those coming up, the individual vaccines. But first I just want to remind you that some kids will come to you and they won’t be up to date on their immunizations. This is a table that’s in the syllabus and shows the catch-up immunization schedule. It just shows some general intervals. These are derived from the routine schedule and you can pretty much figure them out. This is something that you wouldn’t need to memorize but you do need to know when kids are under-immunized, which vaccines are indicated and figure out a schedule for them to get up to date on their immunizations.
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Adolescent immunizations; there’s been a recent push to make the 11-12 year old visit a routine visit in the office for a variety of reasons, and including immunizations, to make sure that adolescents are caught up and up to date with some of the vaccines that may be different from when they were younger, such as make sure they get varicella vaccine. Make sure that they have two doses of MMR vaccine and that they are up to date on the hepatitis B vaccine series. Also you can give them a booster dose of tetanus at that time, and give other vaccines if indicated in special circumstances, such as hepatitis A vaccine, flu vaccine or pneumococcal vaccine.
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We are going to talk briefly about passive immunization. I’ll talk about it more with hepatitis A. But in general, passive immunization is the administration of pre-formed antibody is effective preventing hepatitis A. Gamma globulin, you give that, and you can prevent that if given within 14 days of exposure. And measles within six days of exposure. Intravenous immune globulin, IV IG in general, also contains a wide variety of antibodies and you can use that in the same situation if somebody is getting that for another reason. This will also provide protection just like the IM version.
Now the content of linoleic acid is different in different milks. Human milks contain 3-7% of the calories from linoleic acid. Common formulas contain 10%. Cows milk … see, this is human milk, this is one of the reasons why the cows milk formulas are supplemented. So if you just look at cows milk and fed that to a baby from the very beginning, you would get a baby that would be linoleic acid deficient. They would also be linolenic deficient. That’s why the formulas, which are based on cows milk, have taken and added linoleic acid but they outdo what even the humans, what the mothers produce. They’ve tried to make it a little bit better in this way and give 10% of the calories coming from linoleic acid. But human milk is 3-7%. Again, it’s the kind of thing you might be asked about.
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Recommendation of expert panel on blood cholesterol in children and adults. Greater than two-year-olds, no more than 30% of the total calories should come from fat. Saturated fat, less than 10% of the total calories should come from this. Intake of dietary cholesterol is not to exceed 300 mg per day. I mean, this is what the American Academy of Pediatrics, their panel of experts, says. So they are trying to … I don’t know how many children are following this but this is considered to be a relatively low fat diet. But really it’s quite a decent diet but it doesn’t allow for a lot of junk foods that contain fat.
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Let’s talk about the vitamins. Water soluble vitamins. These are the ones that are considered to be water soluble. So again it’s important to at least recognize them. The deficiency states with the water soluble vitamins; again, one of the typical things to recognize is that thiamin is associated with beriberi. And this is congestive heart failure, tachycardia, and peripheral edema. And the peripheral edema is believed to be associated with the congestive heart failure. So the main manifestation is by heart failure and its consequences. There is a so-called dry beriberi which also can be seen as a manifestation of B1 deficiency, which mainly has neurological manifestations associated with it and is more likely to be a complaint that one would see some of these things in the older children or adults. Again, it’s so uncommon. There are very few youngsters, at least in this country, who have ever experienced this state. But anything is possible. Riboflavin deficiency, clinical presentation; seborrheic dermatitis, hyalosis, photophobia. Be aware that some of these features can overlap with other nutritional deficiencies and you need to be able to separate them out or to show which conditions overlap, as you will see. Pyridoxine deficiency, again vitamin B6 deficiency. In newborns it can present as convulsions. In older children, skin manifestations as well as neurological manifestations, so there is overlap of some of these conditions and you need to be able to separate them out.
In terms of vaccine administration, you’ll see terms such as contraindication and precaution. A contraindication is a strong recommendation against giving the vaccine and it’s very strong because harm may occur to the person you are vaccinating. Whereas the precaution; you need to consider the circumstances and in some cases you may want to give the vaccine, even though there is a precaution against giving it because the benefits of vaccination may outweigh the risks of the vaccine itself. You need to sort of individualize this. There are a few vaccines where this is very important and I will talk about those issues when that comes up for the specific vaccine.
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These are general contraindications for vaccination, and again we are talking generalities now. We’ll talk about the specific vaccines in a moment. But in general, anybody with an acute febrile illness should not be vaccinated. It may interfere with your evaluation of their acute illness in an immunosuppressed individual, or if somebody in the household has an immunodeficiency disorder. We’ll talk about specific vaccines that are indicated just in that circumstance and others that you would want to avoid. Pregnancy; live vaccines in general are contraindicated due to theoretical concerns. Recent passive antibody administration will interfere with parenteral live vaccine take, such as MMR and varicellar vaccine. And anybody with a prior allergic reaction or serious adverse reaction to the same or related vaccine, obviously you’d want to think about giving them the same vaccine again.
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But it’s important not to over-call contraindications. If you over-call them and don’t give a vaccine when it’s indicated, a missed opportunity for vaccination and you shouldn’t do that. You should be aware that these are not vaccine contraindications, but these are common misconceptions. Anybody with a previous mild local reaction or a fever. You give a DTaP vaccine and they have a fever of 101 afterwards, that’s no big deal. Anybody with a mild acute illness, a low grade fever, a kid with a cold, a kid with otitis media, a kid taking antibiotics for otitis media, that’s not a contraindication to vaccination. Recent exposure to an infectious disease such as chicken pox, a penicillin allergy or non-specific allergies are not contraindications. Family history of seizures, SIDS or whatever, it’s not a contraindication. Mother pregnant or breast feeding, a kid with diarrhea, TB, positive PPD or simultaneous PPD – there’s some confusion there – and we’ll talk about that more with MMR vaccine. But those aren’t contraindications. Prematurity in general isn’t a contraindications. We’ll talk about some caveats in relationship to hepatitis B vaccine and malnutrition. So these are not contraindications to vaccination.
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In terms of scheduling immunization, as a general rule, simultaneous immunization is beneficial. You can give as many as you want at one visit. If a lapse in a series occurs, there is no need to restart the series. The body remembers. The immune system remembers that first dose. In general the minimal interval between the first two doses in a series is four weeks, and in general vaccine brands are interchangeable. So although your syllabus, to be complete, contains a lot of trademark vaccine names and a lot of the slides will show that too, don’t pay too much attention to those for Board review purposes. Those are important sometimes for practical purposes, but on a test in general – and I’ll point out some exceptions – in general you don’t have to know the vaccine brands.
Autoimmune disease in children. Well, it’s probably more common than we think. Typically we think of this as a disease affecting adolescent females but we have seen it in boys, we have seen it in little children, even as young as two or sometimes even less. Presentation, again, highly variable. They may turn up with chronic liver disease and all the characteristic usual associations; cirrhosis, portal hypertension. But where we sometimes see it, and it’s very bothersome when it occurs this way, as a cause of actual fulminant liver failure in sub-acute kind of presentation. Some of these little ones will need liver transplantation very rapidly.
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The diagnostic clue is that if you look at the proteins in the blood, the total serum protein is going to be high and the serum albumin is going to be low and the reason for that is that there is a hypergammaglobulinemia. So if you see a low serum albumin, a high total protein and you are beginning to think about chronic liver disease, it might make you think about autoimmune.
Then there is a whole array of diagnostic markers that I am not going to delineate for you; anti-smooth muscle, anti-mitochondrial antibodies, anti-liver-kidney microsomal. You can think about just about any antibody you want to and look for it as part of the way that you prove your diagnosis. Along, of course, with liver biopsy.
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The treatment, particularly if you are savvy and you make this diagnosis early, is immunosuppression. The mainstay is still steroids. You might add 6-MP, azathioprine or even some of the newer immunosuppressants to try and control the process. You have to remember that autoimmune diseases, no matter which one it is, are multi-system diseases so whether the presentation is in the liver or somewhere else, you should look at the joints, you look for funny rashes, you look for ulcerative colitis and Crohn’s disease, diabetes, thyroid problems. So don’t just stop at the liver. Make sure you have really carefully gone through all the other systems that could be involved.
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