Section 1 of the misc.kids Childhood Vaccinations FAQ
Section 2 of the misc.kids Childhood Vaccinations FAQ
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From: gazissax@netcom.com
Newsgroups: misc.kids.info,misc.answers,news.answers
Subject: misc.kids FAQ on Childhood Vaccinations, Part 3/4
Followup-To: misc.kids.health
Approved: news-answers-request@MIT.EDU, kids-info-request@ai.mit.edu
Reply-To: gazissax@netcom.com
Summary: This FAQ contains information on vaccinations, with particular
        focus on the vaccinations given to children.  Section 3 contains 
	information about vaccines which are not on the required schedule
	for children within the USA (though some may be required in other
	countries), or which have been added since 1996.  These include 
	travel vaccines, vaccines which are not yet approved, and vaccines 
	which, within the USA, are given only to people with particular risk 
	factors.

Archive-name: misc-kids/vaccinations/part3
Posting-Frequency: monthly
Last-Modified: October 23, 1999

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Section 3f. Influenza
[This section last updated on October 23, 1999.]

Q3f.1 What is influenza, and what are the risks of the disease?

Influenza has a fairly high mortality rate among the elderly and the chronically ill. Complications include pneumonia, neurological complications, myocardia, heart block, and peripheral vasoconstriction.

Q3f.2 How common is influenza?

Outbreaks of flu occur almost every year, generally in the winter, and can cause thousands to be hospitalized.

Q3f.3 How effective is the influenza vaccine?

About 70-80% in young, healthy adults. About 50% effective in adults over 60. (For studies on older adults, see JAMA 1994 Dec 7, N Engl J Med 1994.) For a summary of recent studies showing benefits in elderly adults, young children in day care, and healthy adults, see Journal Watch for January 1, 1996, Volume 16, Number 1, "Top Medical Stories of 1995." Of particular interest to parents is a study published in Arch Pediatr Adolesc Medicine, Oct 1995, 149:1113, in which children at high risk for otitis media (ear infections) showed 32% fewer cases during the flu season when they received the flu vaccine.

Note that influenza vaccine protects against influenza only, and not against other respiratory infections.

An intranasal flu vaccine has shown efficacy in trials and may be available within a year.

Q3f.4 How long does the influenza vaccine last?

It has to be repeated every year, as the strains of influenza vary from year to year.

Q3f.5 What are some of the risks of the influenza vaccine?

Public confidence in flu shots was reduced by the swine flu controversy of 1976-1977. Of the nearly 48 million people who were vaccinated that year, about 500 came down with a rare paralytic condition called Guillaine-Barre syndrome. This was many more than could normally be expected to come down with this disease (though still a small percentage of all the vaccinated people). After this year, there were changes to the vaccine, and medical sources (Berkeley, PDR) report that the vaccine has not been clearly associated with Guillaine-Barr syndrome since that time.

Adverse reactions include local tenderness, and, infrequently, fever, "most often [affecting] people who have had no exposure to the influenza virus antigens in the vaccine (e.g. small children)." (PDR) Allergic reactions also occur.

Q3f.6 When is the influenza vaccine recommended?

It is recommended for people who are over 65 and for people with various chronic illnesses, particularly those affecting the lungs (including asthma) or the heart. Candidates among children include similar groups to those for pneumococcal vaccine: sickle cell, chronic renal and metabolic disease, diabetes, chronic pulmonary disease, long-term aspirin therapy, and significant cardiac disease (Catalana).

In the US, the rate of vaccination for influenza in the groups for whom the vaccine is recommended is only 20%. Among children, the rate is 1-7% (Catalana).

The antiviral drugs amantadine and rimantadine are also effective against influenza A, but not influenza B.

Q3f.7 When is the influenza vaccine contraindicated?

Egg allergy, hypersensitivity to thimerosal. Delay in case of an active neurological disease or fever. (PDR) The AHFS gives the same contraindications, but adds a history of Guillaine-Barre syndrome and bleeding disorders which would contraindicate intramuscular injection.

Vaccine components capable of causing adverse reactions: chick embryo components, formaldehyde, thimerosal (Travel Medicine Advisor).

Q3f.8 Is it OK to be vaccinated for influenza during pregnancy?

It depends. When this topic has come up on misc.kids, people have reported different recommendations from their doctors. And, when I consulted the PDR, I found the same result: the PDR says that the risks of the vaccine (especially during the first trimester) have to be weighed against the risks of a particular patient getting the flu, and that "The clinical judgment of the attending physician should prevail at all times in determining whether to administer the vaccine to a pregnant woman."

The CDC, in the October 8, 1999 issue of MMWR, recommended that "Pregnant women with high-risk medical conditions should be vaccinated before the start of the influenza season regardless of their stage of pregnancy. Pregnant women without high-risk medical conditions, but who will be in their second or third trimester during the influenza season, are at elevated risk of complications and should be vaccinated. Some experts prefer to vaccinate these women during the second trimester to avoid a coincidental association with spontaneous abortion, which is common in the first trimester, and because exposures to vaccines traditionally have been avoided during the first trimester. "

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Section 3g. Pneumococcal vaccine
[This section last updated September 18, 1999.]

Q3g.1 What is pneumococcal disease, and what are the risks of the disease?

It causes ear infections and sinusitis in children, and sometimes meningitis and pneumonia.

Q3g.2 How common is pneumococcal disease?

From Nelson Textbook of Pediatrics, Behrman and Vaughn, eds.,14th edition,
1992:

------------------------------------------------------------------------
Pneumococcus (_Streptococcus pneumoniae_) is a normal inhabitant of the
upper respiratory tract (as many as 91% of children between 6 mo and 4
1/2 yr of age carry this bacterium at some time). Pneumococcus is the most
common cause of bacteremia (bacteria in the blood), bacterial pneumonia,
and bacterial otitis media (middle ear infections). Pneumococcus causes
25-30% of acute middle ear infections. It is also high on the list for
bacterial causes of meningitis.  
------------------------------------------------------------------------
There has been recent evidence of antibiotic-resistant pneumococci (see JAMA 1994; 271:1831; and MMWR 1994; 43:23; articles summarized in Journal Watch, January 15, 1995 in the paper edition and February 7, 1995 in the electronic edition).

Q3g.3 How effective is the pneumococcal vaccine?

It protects against 23 strains of pneumococcus, 85% of those which cause ear infections and almost all of those which cause pneumonia and meningitis. Harrison's Internal Medicine estimates its effectiveness at 60-80%.

Some recent articles discussing (and debating about) the effectiveness of pneumococcal vaccine can be found in Arch Intern Med 1994 Dec; 154:373, 154:2666 and 154:2531; these articles and others are summarized in "Feature: Does Pneumococcal Vaccine Live Up to Its Reputation?" in the February 28, 1995 Journal Watch (electronic form) or Mar 1, 1995 Journal Watch (print form). Other relevant articles are in the Annals of Internal Medicine 1988;108:616-625 and the New England Journal of Medicine for 11/21/91.

Q3g.4 How long does the pneumococcal vaccine last?

According to a chart I got from Kaiser, one dose is good for life, except for immune suppressed or immunodeficient patients, who should get a booster two years later. _Travel Medicine Advisor_ also says that no booster is required. _AHFS Drug Information_, however, says that antibodies are elevated at least five years in healthy adults, but decline to prevaccination levels after ten years in some.

The reason for the apparent conflict in recommendations is that allergic reactions are more common after the booster shots, but, at the same time, the booster shots are useful for maintaining immunity. For this reason, there has been some debate about the booster shots; the most recent recommendation is "revaccination with pneumococcal vaccine after six years in people with high-risk chronic conditions" (Journal Watch for Oct 18, 1994). (An example is a person without a functioning spleen.) The 23-valent vaccine was introduced in 1993; prior to that the vaccine was only 14-valent.

Journal Watch for Oct 18, 1994 summarizes an article in the Archives of Internal Medicine (1994 Oct 10; 154:2209-14) on pneumococcal boosters. "Antibody levels wane significantly within six years after vaccination, necessitating revaccination of high-risk patients. This interesting study evaluated immunogenicity associated with revaccination." Shots of pneumococcal vaccine were found to increase antibody levels "at least 1.4-fold in about 55 percent" of both previously unvaccinated adults and those who had been vaccinated 5.5 to 9 years previously.

Q3g.5 What are some of the risks of the pneumococcal vaccine?

Discomfort at injection in 30-40% of recipients, and fever in 5-20% of recipients. (Catalana)

Q3g.6 When is the pneumococcal vaccine recommended?

It is recommended for children 2 or older who are at increased risk of pneumococcal infection. Conditions which increase risk of pneumoccoal infection include HIV positive status, functional or anatomic asplenia, and sickle cell or other hemoglobinopathies. It is also recommended for adults 65 or older and adults with significant cardiovascular or pulmonary disorders, splenic dysfunction, asplenia, Hodgkin's Disease, multiple myeloma, cirrhosis, alcoholism, renal failure, CSF leaks, or immunosuppressive conditions.

Work is underway now to develop and test a pneumococcal conjugate vaccine (analogous to the HiB conjugate vaccine) to allow immunization of those younger than 24 months (which is the age group most affected by S. pneumoniae). This might open up a new indication for pneumococcal vaccine: prevention of middle ear infections. As of 1997, four different conjugate pneumococcal vaccines for infants were in Phase II/III trials (Williams, 1997)

Q3g.7 When is the pneumococcal vaccine contraindicated?

It should not be given to children under 2. It also shouldn't be given to people who have already been vaccinated (except for booster shots for those in the highest risk categories).

Vaccine components capable of causing adverse reactions: phenol, polysaccharides, thimerosal (Travel Medicine Advisor).

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Section 3h. Meningococcal vaccine [This section last updated on September 18, 1999.]

Q3h.1 What is meningococcal disease, and what are the risks of the disease?

Meningococcal disease is a rare disease which causes meningitis as well as widespread blood infection, leading to shock and death.

Q3h.2 How common is meningococcal disease?

About 2,500 cases a year in the US, but tens of thousands annually in sub-Saharan Africa.

Q3h.3 How effective is the meningococcal vaccine?

The current vaccine not highly immunogenic in children under 2, or very long lasting, and it is children under 2 who have the highest rate of the disease. Research is being done on conjugate vaccines which would produce a greater immune response. Global cooperation would be needed to make these affordable in developing countries. (Williams, 1997)

Q3h.4 How long does the meningococcal vaccine last?

I don't have this information.

Q3h.5 What are some of the risks of the meningococcal vaccine?

Adverse reactions are infrequent and mild, mostly redness at the injection site for 1-2 days. Up to 2% of children vaccinated will experience transient fever (Health Information for the International Traveller, 1992).

Q3h.6 When is the meningococcal vaccine recommended?

For children with certain types of immune disorders and during epidemic outbreaks. It is also given to children travelling to certain areas, and is required for pilgrims to Mecca for the annual Haj (as of 1992, according to the CDC).

Q3h.7 When is the meningococcal vaccine contraindicated?

I haven't found any, except pregnancy (when it should be given only in case of an outbreak).

Vaccine components capable of causing adverse reactions: phenol, polysaccharides, thimerosal (Travel Medicine Advisor).

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Section 3i. Varicella (chicken pox) vaccine

[Note: The varicella section has been modified slightly and updated. Information is from FDA press releases on 1/28/94 and 3/17/95 and and an article in Infectious Diseases in Children newsletter {vol 8(2) February l995}. It has been further updated based on the July 12, 1996 recommendation by ACIP. This section last updated on September 25, 1999. I have some additional information on zoster which I will be merging into this section in my next update.]

Q3i.1 What is chicken pox, and what are the risks of the disease?

Varicella or chickenpox is a highly contagious disease caused by varicella zoster virus. Complications are rare in normal children, but more common in children with immune deficiencies. The disease is somewhat more severe in adults, and can be serious for newborns and pregnant women. Possible (infrequent) complications include hemorrhagic varicella, encephalitis, pneumonia, and bacterial skin infection. Possible complications in pregnancy include premature birth and congenital varicella, and mortality (of the infant, not the mother) is high. "It is estimated that there are about 9,600 chicken-pox related hospitalizations annually, with 50 to 100 deaths." (FDA announcement, January 28, 1994) Another risk, unfortunately on the increase, is invasive group A streptococcal infections, to which children ill with varicella may be susceptible.

A study of the effects of congenital varicella and herpes zoster (Enders G; et al. Consequences of varicella and herpes zoster in pregnancy: prospective study of 1739 cases. Lancet 1994 Jun 18; 343:1548-51., summarized in Journal Watch Summaries for July 1, 1994.) followed 1373 women with varicella and 366 women with herpes zoster acquired during the first 36 weeks of pregnancy. Nine of the infants had congenital varicella syndrome, with defects ranging from "multisystem involvement to limb hypoplasia and skin scars." There were no cases of congenital varicella syndrome among infants whose mothers had varicella after 20 weeks or among those whose mothers received anti-varicella-zoster immunoglobulin after they were exposed.

Q3i.2 How common is chicken pox?

An estimated 3.7 million Americans are affected by chickenpox each year, with more than 90% of the cases occurring in persons under 15 years of age. 33% of cases are estimated to occur in children ages 1 to 4, and 44% in children ages 5 to 9 (estimates from January 28, 1994 FDA announcement).

In tropical regions, chicken pox is less common, and many people may reach adulthood without immunity (adult immigrants from tropical to temperate regions may therefore be at risk).

I do not have data on how varicella incidence has been affected by the availability of the vaccine, but vaccine coverage is still (as of 1999) fairly low for this particular vaccine.

Q3i.3 What is Herpes Zoster?

Following chickenpox infection, the varicella zoster virus persists in a latent form in sensory nerve ganglia without any signs of illness. The virus can be reactivated causing herpes zoster or shingles, which is a painful small blister-like rash in the distribution of one or more sensory nerve roots. It is estimated that 15% of the population will experience zoster during their lifetimes. Zoster develops most frequently among the elderly and among individuals who are immunocompromised. Most people only have one episode of herpes zoster; fewer than 4% will have repeated episodes. Postherpetic neuralgia is a common complication; this complication is more common among the elderly (25-50% of those over 50 who have shingles, but only 10% of all people who have shingles.

(Information on the effect of the vaccine on herpes zoster will be added to this FAQ later.)

Q3i.4 What is the current recommendation for the chicken pox vaccine be part for children?

The chickenpox (varicella) vaccine was first licensed for use among high-risk children in several European countries in 1984, in Japan in 1986, and in Korea in 1988. It has been used for healthy children in Japan and Korea since 1989. This vaccine was licensed by FDA on March 17, l995. It is manufactured by Merck and Co. Inc. under the trade name "Varivax." On July 12, 1996, ACIP came out with its recommendations for the new vaccine. ACIP recommends that all children be routinely vaccinated at 12-18 months of age. The American Academy of Pediatrics recommends that it be given to everyone over the age of one who is not already immune to chicken pox. Currently it is approved by the FDA for a single injection in children ages 12 months to 12 years, and two injections 4-8 weeks apart for adolescents and adults--ages 13 and older-- who have not contracted chickenpox. Since the vaccine has been shown to be safe and effective when given at the same time as measles, mumps and rubella vaccines, it is likely many physicians will give it either at the 12 or 15 month checkup. Research is underway for development of a combination measles, mumps, rubella and varicella vaccine to avoid the need for a second injection. It is unknown when this product may become licensed.

Q3i.5 What is the current recommendation for adults?

*************************************************************************
[Contributed shortly before the vaccine was licensed.]
From J Thompson (jet14@columbia.edu):

    I think it is almost guaranteed that adults will be able to get the
varicella vaccine. The only area where there is _no_ scientific controversy
over the wisdom of using this vaccine is in adults who are not immune.
Varicella in adults is a dangerous disease, sometimes leading to
hospitalization, and usually lasting two to three weeks.
*************************************************************************
ACIP recommends that people 13 years and older be assessed for varicella immune status, and that those who are not immune be vaccinated. Priority should be given to vaccinating those at highest risk for exposure and for transmitting the disease. There is an antibody titre which can be done on adults who are not sure whether they are immune to chicken pox.

Q3i.6 How effective is the chicken pox vaccine?

Clinical trials, which span a decade and involved more than 11,000 persons in the United States, indicate that it is 70-90 percent effective in preventing chickenpox. Studies also show that almost all of the vaccinated patients who got chickenpox had a milder form of the disease.

Q3i.7 How long does the chicken pox vaccine last?

We don't know yet. It is estimated to last at least six years. (Lancet, April 16, 1994) "Children immunized as long as six years earlier continued to be well protected. . . . So far, the US data show persistence of antibodies for three to four years after immunization; data from Japan show persistence of antibodies for seven to 10 years in healthy children." (Gershon)

Q3i.8 What reactions have been reported following the chickenpox vaccine?

Adverse reactions reported were mild and included redness, hardness and swelling at the injection site, fatigue, malaise and nausea. The vaccine has been used in Japan routinely for more than 10 years with no complications.

Q3i.9 Will a second dose be necessary in younger children?

The question of a "booster" dose remains uncertain at this point. The manufacturer has agreed to perform postmarketing studies to determine the long-term effects of the vaccine and whether there is a need for a booster immunization.

Q3i.10 For which groups is the chicken pox vaccine especially recommended?

People with HIV, nephrosis, severe asthma, and similar chronic diseases, but especially leukemia. Conditions for vaccination of leukemic children are: remission for at least a year, off maintenance therapy for a week before and a week after getting the vaccine, and cellular immunity intact. (Catalana)

Q3i.11 When is the chicken pox vaccine contraindicated?

*************************************************************************
From the April 1995 issue of Medical Sciences Bulletin, published by 
Pharmaceutical Information Associates (pialtd@ix.netcom.com) and 
available by Email subscription as MSB-L.

Use of Varivax is contraindicated for patients who are hypersensitive to any
component of the vaccine; those with a history of anaphylactoid reaction to
neomycin; those with active febrile infections, pregnancy, blood dyscrasias or
other malignancies, or primary or acquired immunodeficiency; and those
undergoing immunosuppressive therapy.
*************************************************************************
The July 12, 1996 ACIP recommendation lists, for the most part, the same groups, but adds people who have experienced an anaphylactoid reaction to gelatin, and people who have a family history of congenital or hereditary immune deficiency in parents or siblings (unless their own immune competence has been clinically substantiated or confirmed by a laboratory). Pregnant women should not be vaccinated, as the effect on the fetus is unknown.

Although no adverse reactions from taking aspirin after the vaccine have been reported, it is recommended that people receiving the varicella vaccine refrain from taking aspirin for 6 weeks afterwards, because of the association between aspirin and Reyes syndrome following varicella.

Q3i.12 Is there a gamma globulin for chicken pox?

Yes, but it is only available to people at especially high risk from chicken pox. It needs to be given within 72 hours of exposure. More common on misc.kids is the concern of adults who haven't had chicken pox, but aren't otherwise at high risk from exposure. The varicella immune globulin isn't likely to be available to these people, but something else is available: acyclovir. This antiviral drug will lessen the severity of chicken pox if it is given promptly, as soon as the rash first begins to appear.

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Section 3j. BCG (tuberculosis) vaccine
[This section last updated on September 25, 1999, based on the ACIP recommendation which was published in MMWR on April 26, 1996, and which can be found at ftp://ftp.cdc.gov/pub/Publications/mmwr/rr/rr4504.pdf]

Q3j.1 What is tuberculosis, and what are the risks of the disease?

Tuberculosis is a chronic bacterial infection that is spread by inhaling droplets sprayed into the air by someone infected with TB (it can also be spread through unpasteurized milk). It isn't as contagious as a cold (you need to inhale a higher concentration of the droplets to catch it). The disease most commonly affects the lungs, the bones of the spine or large joints, and the kidneys, but can reach almost any organ of the body.

Q3j.2 How common is tuberculosis?

In 1930, mortality was 101.5 per 100,000 population in the US. It declined steadily, and in 1970 was 18.3 per 100,1000 population (Historical Statistics). 37.1 thousand cases were reported in 1970, and the number was down to 25.7 thousand in 1990 (Statistical Abstracts). Unfortunately, while that number represents a decrease from 1970, it represents an *increase* from 1985. In 1985, after decades of decline, TB cases began to rise again in the US, and have continued to rise ever since. A similar increase has occurred in several other industrialized countries (TB was never really brought under control in the Third World). Moreover, new, multi-drug-resistant strains of TB have emerged. The AIDS epidemic has worsened the TB situation. (Ryan) The percentage of cases of drug-resistant TB varies in different areas. A Morbidity and Mortality Weekly Report article summarized in the June 15, 1994 HICN726 Medical News gives the incidence overall in New Jersey as 5% of the state's TB patients, the incidence in Jersey City as 13%, and the incidence in New York City as 19%.

A joint statement by ACIP and the Advisory Council for the Elimination of Tuberculosis, published in MMWR, Volume 45, No. RR-4, April 26, 1996 states that the incidence of TB declined through 1984, increased from 1985 through 1992, and declined slightly in 1993 and 1994. 57% of the total number of TB cases were reported in five states: California, New York, Florida, Illinois, and Texas. Overall incidence rates are twice as high for men as for women.

Q3j.3 How effective is the BCG vaccine?

The AHFS Drug Information, 1992 says that its effectiveness is unknown, "Diagnostic and clinical evidence has generally demonstrated a reduction` in the incidence of tuberculosis." Tuberculin sensitivity is highly variable, depending on the strain, and the relationship between tuberculin sensitivity and immunity has not been adequately studied.

_The Forgotten Plague_ says that results of research varied in different countries. In Great Britain, a Medical Research Council survey of 50,000 children showed an 80% reduction in the infection rate after vaccination, leading Great Britain to introduce BCG vaccination of school children in the 1950s. In the US, the results were the opposite, so the US has not used the vaccine.

A New York Times article ("Tuberculosis Vaccine Found Surprisingly Effective in Studies", New York Times, 03/02/94, P. C14), recently reported that "A new statistical study by the Centers for Disease Control and Prevention reports that the vaccine, known as BCG, reduced the risk of full-fledged tuberculosis of the lung by 50 percent and death by 71 percent." A study reported in J Infect Dis in August 1994 concluded that BCG vaccine is effective, but local reactions are common.

The joint ACIP and ACET report in the April 26, 1996 MMWR says that there are different strains of BCG vaccine in use worldwide, and they differ in their ability to induce an immune response to tuberculin. Reported rates of efficacy may also have been affected by methods of vaccine administration and the characteristics and environment of the populations to which the vaccine was given. Protective efficacy rates for different studies of different BCG strains have ranged from 0% to 80%. Two recent meta-analyses of the published literature have attempted to calculate summary estimates of efficacy. The first analyzed data from 10 randomized clinical trials and 8 case-control studies since 1950. It estimated protective efficacy against meningeal and miliary TB in children in clinical trials as 88%, and the efficacy in case-control studies as 75%. There was too much variability in data on efficacy against pulmonary TB for them to come up with a summary efficacy rate. The second meta-analysis reviewed 14 clinical trials and 12 case-control studies. They estimated the overall efficacy of the vaccine in clinical trials to be 51%, with higher efficacy for children than for adults.

Q3j.4 How long does the BCG vaccine last?

It is of limited duration (Ryan). _AHFS Drug Information_ says that several studies showed tuberculin sensitivity lasting 7-10 years.

Q3j.5 What are some of the risks of the BCG vaccine?

It rarely has serious side effects. (See _AHFS Drug Information_ for a list.) The most common reactions are local. More severe local reactions include ulceration at the vaccination site, regional lymphadenitis with draining sinuses, and purulent drainage at the puncture site. The most serious reaction is disseminated BCG infection; BCG osteitis of the epiphyses of the long bones, particularly epiphyses of the legs, can occur from 4 months to 2 years after vaccination. The rate varies from 0.01 cases per million vaccinees, in Japan, to 32.5 and 43.4 cases per million vaccinees, in Sweden and Finland, respectively. Reactions may be more frequent among people with symptomatic HIV infection.

*************************************************************************
From J Thompson (jet14@columbia.edu):

    The main strategy of TB control in the US is monitoring those at risk of
exposure to the disease for signs of TB infection. The main method used is
something called a "PPD" (which stands for purified protein derivative, i.e.
proteins purified from TB). A PPD is "placed" (injected subcutaneously) and
then the site of injection is monitored (usually at 48 hrs. after the
injection). Anyone who has mounted an immune response to a TB infection will
exhibit redness and swelling at the site of the PPD injection (the criterion
for calling a "true positive" PPD is that the inflammation must be at least
10 mm. wide). Also, this reaction must take place at a 1-2 day delay to be
diagnostic for TB infection (anything sooner is allergy, not a sign of
infection).
    OK, what does all this have to do with BCG? Well, BCG, since it is very
similar to TB, can cause a positive PPD. Thus, widespread immunization with
BCG makes it more difficult to screen for TB, since the screening will pull
up many people who are not infected. The reaction due to BCG drops over
time, but it is still a problem, so that (combined with the low
effectiveness) has ruled out BCG in the US. Of course, now that
drug-resistant strains are becoming more common, opinions might change...
*************************************************************************
Q3j.6 When is the BCG vaccine recommended?

BCG vaccine is given in developing countries because it is easy to administer, inexpensive, and rarely has serious side effects. Some industrialized countries (e.g. Great Britain, France, Scandinavia) have also used it, for vaccination of children in general and of household contacts of people with TB. Others (e.g. the US, the Netherlands) have not.

Because of the low rate of new infections, the availability of low-cost isoniazid prophylaxis for people who are exposed, and the availability of effective treatment which quickly make patients non-contagious and cures them, the BCG vaccine hasn't been considered necessary in the US. There might be some changes in these recommendations with the increase in multiple-drug-resistant strains (one misc.kids poster reports that her city college system is now requiring TB shots). In the meantime, the FDA has approved a new combination tuberculosis drug, Rifater, which combines isoniazid, rifampin, and pyrazinamide, in hopes of making it easier for patients to take their medication and thus increasing patient compliance (antibiotic treatment which is discontinued too early increases the development of drug resistant TB strains).

In the US, the AAP, ACIP, and the American Thoracic Society recommend BCG for infants and children intimately exposed to TB that is "persistently untreated, ineffectively treated, or resistant to isoniazid and rifampin and who cannot be removed from the source of exposure or placed on long-term preventive therapy." The AAP and ACIP also recommend it for children in groups with a rate of new TB infections greater than 1% annually "and for whom the usual surveillance and treatment programs have failed or are not feasible." (_AHFS Drug Information_) ACIP also recommends vaccination for children who are continually exposed to a patient who is infected with a strain of TB which is resistant to isoniazid and rifampin (MMWR, April 26, 1996). It is recommended for travel only for people who will be in a high risk environment for a long time without access to TB skin testing. It is currently not recommended for health care workers (skin testing and isoniazid is considered to be enough), but this recommendation is periodically reevaluated because of the incidence of TB in AIDS patients.

BCG also has some use against certain tumors (in particular, bladder cancer).

*************************************************************************
From J Thompson (jet14@columbia.edu):

    The TB "shots" a poster on misc.kids referred to ("one misc.kids poster
reports that her city college system is now requiring TB shots") are most
likely PPD, not BCG. I believe that all schools receiving federal funding
(and I know that all schools I have attended) require either a PPD or the
(less accurate but easier to administer) "tine test" as part of the
pre-matriculation physical.
*************************************************************************
Q3j.7 When is the BCG vaccine contraindicated?

Hypersensitivity to the vaccine, positive TB skin test, recent smallpox vaccination, burn patients, various immune deficiencies or immunosuppressive therapy (see _AHFS Drug Information_ for a list). In case of eczema or other skin disease, give it in a different area of the skin. Although no harmful effects to the fetus are associated wtih BCG vaccination, its use is not recommended during pregnancy.

Vaccine components capable of causing adverse reactions: Triton WR 1339 (Travel Medicine Advisor).

Q3j.8 What are some other methods of controlling tuberculosis?

Tuberculin skin screening and use of drugs such as isoniazid. Pasteurization of milk and testing of cows for tuberculosis are also useful.

===============================================================================
Section 3k. Hepatitis A

[Hepatitis A: The following was taken from an article in JAMA (March 22/29, l995--Vol 273 (12) 906-907) and information from the *draft* hepatitis A vaccine recommendation which was, as of April l995, under consideration by the ACIP It has since been updated based on the ACIP and AAP recommendations as of December 1996, the CDC Vaccine Information Statement on hepatitis A as of 8/25/98, and articles at Medscape. This section last updated September 19, 1999.]

Q3k.1 What is hepatitis A and what are the risks of the disease?

There are several forms of hepatitis (infection of the liver) which cause jaundice, nausea and weakness. Hepatitis A is caused by infection with hepatitis A virus (HAV) which is acquired primarily through a fecal-oral route, most often from person to person. It can also occur via ingestion of contaminated food or water. The illness consists of mild flu-like symptoms or severe nausea lasting for weeks. Hepatitis A does not become chronic and is rarely fatal. In children under 6, most cases (>70%) of hepatitis A are asymptomatic, and if illness occurs, it is usually not accompanied by jaundice. Among older children and adults, the illness is usually symptomatic, and jaundice occurs in >70% of cases. Symptoms usually last for <2 months, but 10-15% of people infected have illness or relapses for up to 6 months. 11-22% of people who have hepatitis A are hospitalized, and hepatitis A is responsible for an estimated 100 deaths a year (these numbers from the ACIP recommendation on hepatitis A - the AAP recommendation gives similar, but not identical, numbers).

Hepatitis A should not be confused with hepatitis B, which is less contagious but more serious. Hepatitis B becomes chronic in 5-10% of those infected. Complications include hepatic necrosis, cirrhosis of the liver, chronic active hepatitis, and hepatocellular carcinoma.

Some sources of general information on hepatitis can be found in the hepatitis B section of this FAQ.

Q3k.2 How common is hepatitis A?

During the past several decades, the incidence of hepatitis A in the U.S. has been cyclic, with nationwide epidemics occurring every 10-15 years; the last occurred in l989. Between epidemics, hepatitis A continues to occur at relatively high levels. Nationally, CDC estimates that around 75,000 cases occur annually. Children play an important role in HAV transmission, with highest rates among those aged 5-14 years. Rates are substantially higher, in the Western US states than in other US regions. The highest rates of hepatitis A are among children 5-14 years of age. In the US, 33% of the population has evidence of prior hepatitis A infection, as determined by a survey conducted from 1988-1991 (reported in the ACIP recommendation for hepatitis A). Prevalence is generally higher among Native Americans and Mexican Americans. Hepatitis A is the most common vaccine preventable illness among travelers. It can be avoided by avoiding contaminated food and drink, but many travelers succumb to temptation, assume food at hotels is safe, buy from street vendors, etc. Incidence is 1.6 per 1000 person-months of travel among travelers to developing countries (including those who stay in luxury hotels), and 20 per 1000 among backpackers and others who eat and drink in poor hygienic conditions. Incidence is 0.05 to 0.10 per 1000 person-months of travel in Southern Europe. (JAMA Sept 21, 1994 p. 885)

Q3k.3 Who is at risk for acquiring hepatitis A?

International travelers and individuals residing in hepatitis A endemic areas are at risk for acquiring disease. Other risk groups include homosexual men, injecting drug users, hemophilic patients, veterinary workers and certain research occupations working with infected animals (particularly people working with non-human primates). Workers at day care centers, institutions for the developmentally disabled, food service establishments and healthcare settings are also at some increased risk.

Q3k.4 Is there a vaccine to protect against hepatitis A?

Yes, the FDA licensed the hepatitis A vaccine for use in persons 2 years of age and older on February 22, l995. An ACIP recommendation was published in the MMWR for December 27, 1996. The American Academy of Pediatrics also published a policy statement in December 1996. The vaccine has been in use in Europe since 1992.

Q3k.5 How is it to be administered?

According to the labeling, the vaccine is given in a two-dose schedule to adults 18 years of age and older, the second dose being given 6-12 months after the first. Children and adolescents 2-18 years of age are given 3 doses. The second dose is given 1 month after the first and the third dose 6-12 months later. It is administered by intramuscular injection in the deltoid (upper arm), and can be given with other vaccines without loss of immunogenicity.

Q3k.6 How effective is the vaccine?

A single dose of the vaccine induced antibodies in 88% to 96% of subjects by two weeks and in 97% to 100% by one month. Completion of the full vaccine schedule is recommended to ensure high antibody levels and long-term protection. Efficacy trials in children and adolescents show it is 94% (or more) effective against endemic hepatitis A virus.

According to the AAP recommendation for hepatitis A, on December, 1996: "Clinical studies suggested a possible herd-immunity effect if more than 80% of the estimated susceptible individuals were vaccinated. A single dose of Havrix in Alaskan native villages with endemic HAV disease resulted in a dramatic decrease in cases within 8 weeks of vaccination. A similar abrupt decrease in HAV cases was observed after two doses of vaccine in two Slovak Republic villages experiencing a large community outbreak. In the Vaqta trial in New York State, no cases of clinical and confirmed hepatitis A occurred in vaccine groups more than 21 days after the first dose, and the calculated protective efficacy was 100%. "

Q3k.7 How long does immunity last?

Firm data on long-term protection are limited because the vaccine was under investigation for only 4 years before being approved in 1995. Estimates of antibody persistence derived from kinetic models of antibody decline suggest that the protective levels of anti-HAV could persist for at least 20 years.

Q3k.8 What are some of the risks of the vaccine?

Information on adverse events comes from prelicensure clinical studies worldwide and reports following vaccine licensure in Europe, the US, and Asia. No serious adverse events have been attributed to the vaccine. Side effects include soreness and redness at the injection site, headache and fatigue. In very rare cases, there is a severe allergic reaction within a few minutes to a few hours of the shot.

Q3k.9 When is hepatitis A vaccine contraindicated?

The vaccine should not be administered to persons with a history of hypersensitivity reactions to any of the vaccine components, including alum or the preservative (2-phenoxyethanol). Because it is inactivated, no special precautions need be taken when vaccinating immunocompromised individuals. The inactivation also means that they theoretical risk to a fetus is low, but there are no data to determine the safety of the vaccine during pregnancy. People mildly ill at the time of vaccination may get the vaccine, but people moderately to severely ill should wait until they recover.

Q3k.10 What groups at risk are be included in a recommendation to receive hepatitis A vaccination?

ACIP recommends the vaccine for:

1. Persons 2 years of age or older traveling or working in countries with high or intermediate endemicity of infection. The vaccine series should be started at least one month before travelling.

2. Persons living in communities with high rates of HAV infection; for example, American Indian, Alaska Native, Pacific Islander, and some religious communities.

3. Men who have sex with men.

4. People who use street drugs (injected or non-injected).

5. People who work with hepatitis A infected primates or with hepatitis A in a research setting should be vaccinated. No other groups have been shown to be at increased risk for hepatitis A due to occupational exposure.

6. Persons with chronic liver disease.

7. Persons who use clotting factor concentrates.

8. Since people who work as food handlers can contract hepatitis A and pass the disease to others, they may be vaccinated in areas where state and local health authorities determine such vaccination to be cost effective.

The AAP recommends the vaccine for the first six of the groups listed above, and suggests consideration of potential use for child care center staff and attendees, custodial care institutions, hospital personnel, food handlers, and people with hemophilia.

In 1999, ACIP recommended hepatitis A vaccine for all children aged 2 years and older in the 11 Western states where incidence is especially high (at least 20 cases per 100,000 people, twice the national average). These states are: Arizona, Alaska, California, Idaho, Nevada, New Mexico, Oklahoma, Oregon, South Dakota, Utah and Washington.

Any healthy individual 2 years of older may receive hepatitis A vaccine at the discretion of the physician and patient or parent.

Q3k.11 Is it possible that hepatitis A vaccine (like hepatitis B vaccine) might eventually be recommended for routine administration to children and adults?

Those in public health say that control of hepatitis A infection will be facilitated by the development of vaccines that combine hepatitis A with other routine childhood immunizations. The CDC's draft statement notes the important role of children in hepatitis A transmission, and that "it is likely that routine childhood vaccination will be the only way to significantly decrease hepatitis A rates in the U.S."

===============================================================================
Section 3l Rotavirus vaccine
[This section last updated on October 23, 1999.]

Q3l.1 What is rotavirus, and what are the risks of the disease?

Rotavirus is one of the major causes of gastroenteritis among infants and small children in most countries. Symptoms are fever, vomiting, diarrhea, and dehydration, with vomiting and dehydration more common than with other diarrheas. The illness normally lasts 3-9 days, and becomes chronic only in immunodeficient children.

Group A rotavirus is a major cause of infant mortality in many parts of the world. 873,000 infants and children under 5 die per year of rotavirus in developing countries. Non-group A rotavirus is less frequent, and is epidemic only in China. In tropical climates, rotavirus infection occurs year round, while in temperate climates it is seasonal. Rotavirus can survive for hours on human hands and for days on inanimate surfaces, and resists common disinfectants.

Rehydration therapy makes death infrequent in developed countries. On the other hand, it is one of the most common causes of hospitalization among infants during the winter months. Cecil Textbook of Medicine estimates that it is responsible for 35-52% of the cases acute diarrheal illness needing hospitalization in infants and young children, in US.

Q3l.2 How common is rotavirus?

The AAP Committee on Infections Diseases estimates that rotavirus is responsible for 3 million cases of diarrhea, 50,000 hospitalizations, and 20 to 40 deaths each year in the United States.

Q3l.3 What is the current status of the rotavirus vaccine?

On October 15, 1999, Wyeth Lederle Vaccines announced that it has withdrawn its RotaShield vaccine from the market and has requested the immediate return of all doses of the vaccine. The company's press release can be accessed at the web address below. http://www.ahp.com/releases/wa_101599.htm

A brief history of the release and withdrawal of this vaccine follows.

After years of research (animal studies beginning in 1983, and human trials in 1987) into an effective rotavirus vaccine (with a couple of candidates being rejected), a live, oral, tetravalent rotavirus vaccine was approved by the FDA on August, 1998. This vaccine is composes of one rhesus monkey virus, and three genetically engineered combinations of rhesus monkey and human rotavirus. In the December, 1998 issue of Pediatrics, the AAP Committee on Infections Diseases recommended that the vaccine be added to the standard vaccination schedule, with shots being given at 2, 4, and 6 months, with the understanding that it might take time to incorporate the new vaccine into the schedule.

On July 18, 1999, US health officials recommended postponement of rotavirus vaccine. Shipments have temporarily been suspended. The company which makes the vaccine is working with the CDC to investigate reports of bowel obstruction among infants who received the vaccine. An additional reason for postponement was the fact that the rotavirus season, in the US, occurs during the winter, allowing several months for investigation of these adverse reactions, before a decision needed to be made about whether the vaccine should be used prior to this year's rotavirus season. Results of a case-control study were expected to be available by October, 1999. Additional studies could continue into next year. Further information from the CDC about rotavirus vaccine and intussusception can be found at http://www.cdc.gov/nip/Q&A/genqa/Rotavirus.htm and at http://www.cdc.gov/nip/news/rotavirus.htm.

Q3l.4 How effective is the rotavirus vaccine?

Although the rotavirus vaccine has been withdrawn as of October, 1999, I am retaining the answer to this question, in case it should be later reintroduced in some form.

The rotavirus vaccine doesn't confer full immunity, but protects against severe illness (this is also the case with natural immunity from prior rotavirus infections). Trials by the manufacturer, used for FDA approval, showed the following results:

Trial 1: None of the infants receiving the vaccine got dehydrated, compared to 3% in the placebo group. 11% fewer in vaccine group needed a visit to the doctor. 88% showed elevated IgA titers.

Trial 2: 9% of infants in placebo group saw a doctor for diarrhea and vomiting, compared with 2% in vaccine group. None in the vaccine group needed hospitalization.

Both trials were by the manufacturer, and not published in the medical literature at the time of approval.

A third trial, in Finland, showed similar results.

Q3l.5 Is the rotavirus vaccine effective for breastfeeding infants?

Although the rotavirus vaccine has been withdrawn as of October, 1999, I am retaining the answer to this question, in case it should be later reintroduced in some form.

For infants receiving the full three doses, breastfeeding infants show the same level of immunity as formula-fed infants. For infants receiving only one dose, immunity may be less among breastfed infants.

Q3l.6 How long does the rotavirus vaccine last?

Although the rotavirus vaccine has been withdrawn as of October, 1999, I am retaining the answer to this question, in case it should be later reintroduced in some form.

Efficacy persisted for two years in US and Finnish trials. Since followup has only been done for two years, it is not known whether efficacy persists beyond that time.

Q3l.7 What is intussusception?

Intussusception is a bowel obstruction in which one segment of the bowel becomes enfolded within another segment.

Q3l.8 What is the relationship between the rotavirus vaccine and intussusception?

15 cases of intussusception, possibly associated with administration of the rotavirus vaccine, have been reported to VAERS. These cases were analyzed in "Intussusception Among Recipients of Rotavirus Vaccine -- United States, 1998-1999," MMWR 48(27);577-581, 1999, Centers for Disease Control.

VAERS reports of intussusception were reviewed, and parents or guardians or health-care providers contacted by phone for clinical and demographic data. Data on vaccine distribution was also obtained from the manufacturer.

13 of the 15 developed intussusception after the first dose, and 12 of the 15 developed symptoms within a week of receiving any dose. Intussusception confirmed radiologically in all. 8 needed surgical reduction. All recovered. 14 were spontaneous reports, and one was obtained through active postlicensure surveillance. According to the report, "The manufacturer had distributed approximately 1.8 million doses of RRV-TV as of June 1, 1999, and estimated that 1.5 million doses (83%) had been administered. Given this information, 14-16 intussusception cases among infants would be expected by chance alone during the week following receipt of any dose of RRV-TV.

As part of a preliminary analysis of postlicensure adverse events, cases of intussusception during December 1, 1998-June 10, 1999 were identified in Northern California and Minnesota, and the rate in vaccinated and unvaccinated children was compared. Vaccinated children showed a statistically higher incidence of intussusception.

A further announcement by the FDA, made on September 14, 1999, reported that the number of cases of intussusception that may be related to the rotavirus vaccine (15 as of July 7), is now up to 99, including two deaths. The FDA's Dr. Kathryn Carbone, one of the initial reviewers of the rotavirus data, reported to a gathering of the FDA's Vaccines and Related Biological Products Advisory Committee that all these cases are still under investigation, and it is not clear yet whether the two deaths or the other cases were caused by the vaccine.

Further study is being done.

Q3l.9 Why was a connection between the rotavirus vaccine and intussusception not observed prior to FDA approval of the vaccine?

Approval by the FDA only requires trials on about 5,000-10,000 subjects. Rare reactions to a new drug or vaccine will therefore be unknown at the time of FDA approval.

Q3l.10 What other reactions have been reported following the rotavirus vaccine?

Although the rotavirus vaccine has been withdrawn as of October, 1999, I am retaining the answer to this question, in case it should be later reintroduced in some form.

Mild, fever, for usually less than 24 hours. Fever after the first dose is more common in older children, for which reason it is recommended that the vaccination series be begun by the time a baby is six months old. All doses should be given by 12 months, because data regarding the safety and efficacy of vaccine administration to older children are not available.

Irritability, decreased appetite, and decreased activity, were reported more often than with the placebo for five days. Diarrhea was not reported more often than with the placebo.

Q3l.11 Can the rotavirus vaccine be effectively used in developing countries?

Price may be the major barrier, as it is one of the more expensive vaccines (and not likely to get cheaper if any modified version is reintroduced later).

Q3l.12 When is the rotavirus vaccine contraindicated?

Although the rotavirus vaccine has been withdrawn as of October, 1999, I am retaining the answer to this question, in case it should be later reintroduced in some form.

The rotavirus vaccine should not be given in case of: Infants with hypersensitivity to aminoglycoside antibiotics, amphotericin B, or monosodium glutamate that are components of the vaccine, or an anaphylactic reaction to a previous dose of the rotavirus vaccine.

Until further data are available, this live-attenuated vaccine should not be given to children who are immunosuppressed or immunodeficient. Babies of women who are HIV-infected should not get the vaccine unless these babies have tested as HIV-negative at the age of two months or older.

The rotavirus vaccine should be postponed in case of: Acute vomiting and diarrhea (efficacy is uncertain in this case). Moderate or severe fever.

The rotavirus vaccine may be given in case of: Breastfeeding, premature birth, and low grade fever. The vaccine can be given at same time as DTaP or DTP, HiB, hepatitis B, or IPV/OPV, and there is no need to adjust the timing for antibody-containing blood products. Infants living with people known or suspected to be immunocompromised may be immunized.

===============================================================================
Section 3m. Other vaccines which are available
[This section last updated September 17, 1999.]

Q3m.1 What other vaccines are available and when are they given?

Other vaccines available include vaccines for cholera, Japanese encephalitis, typhoid, yellow fever, rabies, plague, Lyme disease, and anthrax. _Travel Medicine Advisor_ also mentions a vaccine for typhus, but, according to the 1996-1997 edition of the CDC Yellow Book (CDC Health Information for International Travel), "production of this vaccine has been discontinued in the US and there are no plans for commercial production of a new vaccine." Since other countries may offer typhus vaccination (though, to the best of my knowledge, it is not required for travel to any country), I am drawing information for this vaccine from a German web site. Immune globulins are also available for a variety of diseases.

For more information on these other vaccines, check the _American Hospital Formulary Service Drug Information_ (a better source than the PDR in this case) and _Health Information for Travelers_, which is put out by the CDC every year (vaccination and booster schedules for all of these vaccines can be found there, as can information on where these diseases are common and what vaccination requirements various countries have for entrance). The latter can be purchased from the Superintendent of Documents, U.S. Government Printing Office, Washington, D.C. 20402, and most local health departments have a copy which can be consulted, sometimes by telephone. It can also be found in some public libraries. The CDC also has a Worldwide Web site which can be accessed for travel information: http://www.cdc.gov/. The International Association for Medical Assistance to Travellers (IAMAT), which has affiliated institutions in over 115 countries, puts out a _World Immunization Chart_. The address of the U.S. affiliate is IAMAT, 736 Center Street, Lewiston, N.Y. 14092. The World Health Organization produces a publication on international travel; it is called _INTERNATIONAL TRAVEL AND HEALTH: Vaccination Requirements and Health Advice_, and copies may be ordered from WHO Distribution and Sales, CH-1211, Geneva 27, telephone (41 22) 791 2476; fax (41 22) 788 0401. The price is 15 Swiss Francs; in developing countries: 10.50 Swiss Francs. Further information about rabies can be found in books on mountaineering and spelunking (the one I consulted is _Medicine for Mountaineering_, by James A. Wilkerson, M.D.). Hepatitis B, hepatitis A, and meningococcus vaccines are given for travel, so people interested in travel vaccinations may want to check the sections of this FAQ dealing with those vaccines.

Anthrax vaccine, in the US, is mainly used by the military as a protection against biological warfare; small quantities are also made available to people with an occupational exposure, such as veterinarians and lab workers. Since vaccines given by the military to soldiers are outside the scope of a FAQ primarily concerned with vaccines which might be given to children, I will not be discussing the anthrax vaccine further.

Cholera is an intestinal infection spread by contaminated food and water. Cholera vaccination is about 25-50% effective in reducing clinical illness for 3-6 months after vaccination (with the greatest protection during the first two months). (_Health Information for Travellers_ gives the effectiveness as 50%, and AHFS Drug Information gives it as 25-50%.) Boosters are every six months for travelers who will be staying for a long time in cholera-endemic areas. Serious reactions are rare. Since the effectiveness is so low, neither the CDC nor the WHO actually recommends the vaccine, but some countries require it. According to AHFS Drug Information, "_Cholera vaccine does not prevent transmission of infection_, and should not be used to manage contacts of imported cholera cases or to control the spread of infection."

Vaccine components capable of causing adverse reactions: bacterial components (Travel Medicine Advisor). The vaccine should not be given to children under 6 months.

Japanese encephalitis B vaccine, licensed in 1993, is given to travelers "who expect to go beyond the usual tourist routes or to spend extended time in rural areas in disease endemic regions" (Harrison's) Its efficacy is estimated at 80-90%. Anaphylactic and severe delayed allergic reactions are common, so people who receive this vaccine should be observed for ten days.

Lyme disease vaccine, licensed on December 21, 1998, is licensed (as of September, 1999) only for people 15 years or older, though that age limit may soon be eliminated. It is recommended for adults and older teens who spend lots of time outdoors in Lyme-endemic areas. You should still protect yourself against ticks if using the vaccine, both because the vaccine isn't 100 per cent effective and because ticks also carry other diseases. In a randomized, double-blind, multicenter trial involving 10,936 people living in the northeastern and upper north central United States, the vaccine efficacy at preventing Lyme disease was 50% (MMWR, January 22, 1999 / 48(02);35-36,43). The duration of immunity is unknown. Side effects included local reactions, transient myalgia or arthralgia, influenza-like illness, fever, and chills.

It is unlikely that your child will ever need a plague vaccination. The disease is found among rural rodents in some areas, including the Western third of the US, but urban outbreaks are now rare. Vaccination is only recommended for people at increased risk due to research or field activities in epizootic areas. An alternative for people at increased risk is tetracycline prophylaxis. _AHFS Drug Information_ gives the vaccine's effectiveness as 90% for 6-12 months. Other measures for avoiding plague in epizootic areas are getting rid of wild rodent food and shelter, defleaing dogs and cats weekly, avoiding sick or dead rodents, and routine bacteriologic precautions in labs.

Vaccine components capable of causing adverse reactions: phenol, beef protein, soya, casein (Travel Medicine Advisor).

Rabies, an almost universally fatal disease transmitted by saliva and brain tissue of infected animals, is rare in the US but more common in some countries where pet vaccination is not common. Dogs are the main reservoir in developing countries, but all animal bites should be evaluated. The most common animal vectors in the US are carnivorous small animals (such as skunks, racoons, foxes, coyotes, and bobcats) and bats. There has been a recent increase in racoon rabies in the mid-Atlantic and northeastern states of the US (MMWR 29 Apr 1994), and programs to institute oral rabies vaccination of racoons, foxes and coyotes have been initiated in some state (similar programs have been used to control fox rabies in Canada and Europe). More than 50% of rabies cases in the US come from exposure to rabid dogs outside the US. The disease is most commonly spread by animal bites, but can also be caught through non-bute exposure, including contact between infected saliva or brain tissue and pre-existing cuts, scratches, open wounds, or mucuous membranes. There are also cases of aerosolized transmission in medical laboratories and caves inhabited by rabid bats, and transmission through cornea transplants from people who had died of undiagnosed (before the transplant) cases of rabies. The chance of infection is more likely in case of bite or non-bite exposure to the head, neck, face, shoulders, or hands, than with similar exposure to the trunk or legs.

In case of exposure to rabies, the wound should be immediately and thoroughly cleaned with soap and water. "Although not included in the ACIP recommendations, some clinicians also rinse the wound thoroughly with water or 0.9% sodium chloride solution and then cleanse with a topical antiseptic (e.g. povidone-iodine)." (AHFS Drug Information 1992) It is also important to promptly vaccinate anyone exposed to rabies (and give rabies immune globulin if the person has not been previously vaccinated), as the disease is, for all practical purposes, always fatal once rabies symptoms begin to show up. (A few people have recently survived after symptoms appeared, but they all had serious brain damage.) Pre-exposure vaccination is given to people who live in or visit rabies endemic areas and to people whose professions or activities put them at extra risk, such as lab workers, veterinarians, and spelunkers. The highest travel risk is where dog rabies is still endemic.

There is some drug interference between chloroquine (an anti-malarial drug) and rabies vaccine, but intramuscular injection can take care of the problem. Need for boosters depends on risk category, and ranges from regular tests of antibody levels every six months, with vaccination when they drop, for rabies lab workers, to no pre-exposure vaccination for most people. Post-exposure, unvaccinated people get rabies immune globulin and rabies vaccine, while previously vaccinated people get rabies vaccine alone, in a smaller amount. Adverse effects include local reactions (30-74% of vaccinees) and mild systemic reactions (e.g. headache, nausea, 5-40% of vaccinees). About 6% of vaccinees have a reaction characterized by urticaria, pruritis, and malaise. Rarely, anaphylactic shock may occur. Because rabies is so deadly, pregnancy is *not* a contraindication to postexposure vaccination.

Vaccine components capable of causing adverse reactions: neomycin, phenol red, thimerosal (Travel Medicine Advisor).

The following posting from sci.med, by Achim Lohse, provides further information about rabies vaccine (the side effect under discussion is anaphylactic shock):

----------------------------Original message----------------------------
...

In Canada (at least as of two years ago) there is only one rabies
vaccine availble, and the manufacturer supplies it only in one-millitre
vials, with strict instructions to use the entire vial for one injection
only.  At $60 + per vial, the series of three costs over $180.  I was
fortunate to have a physician who had worked among fur trappers up north,
and had some familiarity with the vaccine.  He informed me that  if
injected  _intra_dermally, a dose of only 0.1 millilitre is enough.
I confirmed this with the local public health nurse, who showed me that it
had been standard public health procedure in British Columbia for five
years to use the 10% dose intradermally (10 trappers would arrange to
share the contents of a standard vial).

Later investigation via Medline showed that this particular vaccine
human diploid cell (HDCV) is not only the most expensive to produce,
but may also have a significantly higher rate of side-effects when
compared to the much less expensive purified chick embryo vaccine.

I had a taste of physician non-acceptance when my physician was away
after administering the first in the series of three shots.  He assumed
any of the other five doctors in the rural practice could and would complete
the series.  NOT!  I was turned down flat by the two experienced doctors
on duty, and had to get my shot from the public health nurse.

Rabies antibodies (assuming the initial titres are adequate) are considered
to be reliably adequate for only three years, after which a booster is
required (and with the HDVC adverse reactions have most often been
experienced with the booster).  The alternative is to get a Rabies titre
test, but I understand (anyone have figures?) that this is quite expensive,
and in Canada's health system, may simply not be available on demand in
some provinces (unless you can persuade a sympathetic public health official
of the need).

>However, since it's unusual for people to get rabies and the
>vaccine does work fine after exposure, it will probably not be
>part of the usual childhood vaccines.
>
>Mike K

As someone noted in a previous post, the urgency of treatment depends on
the proximity of the infection site to the brain.  A report from a
researcher from pre-war Yugoslavia (Zagreb) indicated that there wolf
attacks resulting in bites to the face and neck have resulted in death,
due to inability to get the antibody titres high enough in time. One possible
strategy to improve this situation (suggested to me by Richard Passwater's
book "Selenium as Food and Medicine") is to take a large dose of selenium
concurrent with or within a few hours of vaccination.  He reports that this
 has greatly increased antibody titres  with other vaccines.

Finally, aside from the risk of not being able to get to treatment in time
after clear exposure, there is the very real danger of unnoticed infection,
expecially in children, by having a cut  finger or lip, etc. come in contact
with saliva from the tongue or coat of an infected animal.  There is even
one reported instance of a spelunker dying after supposedly no other exposure
than inhaling  saliva droplets from rabid bats.  Since unvaccinated victims
can't be treated successfully once symptoms appear, pre-vaccination is the
only available protection for this last type of exposure.

Achim

lohseach@max.cc.uregina.ca   achim.lohse@f45.n140.z1.fidonet.org
------------------------------------------------------------------------

From: Achim Lohse 
Subject:      rabies vaccine - update

Hi Lynn. I did a little more reasearch on rabies vaccine in the past two
days, and learned that the Canadian manufacturer - Connaught Labs, also
markets the vaccine in the U.S..  In fact, it markets two versions in the
U.S., both are human deploid cell vaccines (HDCV), but one, called
"Merieux" is marketed in a 0.1 ml format for intradermal injection.  In
Canada, ironically, this form is not available, and only the 1 ml
intramuscular form is marketed (suggested retail about CDN$75 per vial).

I wasn't able to get any us prices, but was given a U.S. information number:

1-800-VACCINE , which of course, doesn't work from my (Canadian) calling area.

I wasn't able to learn whether HDCV is the still the _only_ type of rabies
vaccine available in the U.S. (it is the  only typpe in Canada).

Finally, I learned that there are two methods of testing rabies antibody titre
(to find out if you need a booster).  The preferred one is the
neutralization assay type, in which diluted serum is mixed with infected
cell culture and checked for reaction.  The titre is reported as the highest
dilution ratio that provokes a reaction, with 1:32 being the minimal
acceptable titre.  If titre is at 1:32, then retesting or boosting is
adviseable in a year to maintain adequate protection.  I couldn't get
any details about the other method, called complement fixation, except that
the local expert considered it less reliable. BTW - for Alberta and
Saskatchewan (and possibly other Canadian provinces) all rabies titre testing
is done by the _Ontario_ Provincial Laboratory, so it's a slow and costly
undertaking.

regards,

Achim

lohseach@max.cc.uregina.ca

------------------------------------------------------------------------
Smallpox vaccine is no longer given, because smallpox has been eliminated by vaccination. The virus is currently kept in labs in the US and Russia, just in case it is needed at some point (there has been talk of destroying the last samples, but the virus recently got a reprieve). Since the elimination of smallpox is one of the major triumphs of vaccination, which is mentioned in many medical texts which I consulted as an argument in favor of vaccination, I'll also mention at this point that smallpox mortality was 25-30%, that it infected 90% of the population at risk, and that there were 10-15 million cases worldwide as recently as 1967. The last natural case was reported in 1977, and the last cases were reported in 1978, as a result of an escape of the virus from a lab (the lab director committed suicide while under quarantine). (Kiple) The only people who still need to be vaccinated for smallpox are the people who work in the labs where the virus is kept.

Vaccine components capable of causing adverse reactions: polymyxin B, streptomycin, chlortetracycline, neomycin, phenol, brilliant green dye, glycerin (Travel Medicine Advisor).

Typhoid is spread by contaminated food and water. The vaccine protects 70-90% of recipients. There are two forms of the vaccine: oral (live), and parenteral (killed). The oral vaccine shouldn't be given to immune-compromised people. Otherwise, there are few adverse reactions, mostly local discomfort and sometimes fever and malaise. Boosters are every three years for parenteral and five years for oral vaccine.

Vaccine components capable of causing adverse reactions: phenol, bacterial components (Travel Medicine Advisor).

The following posting from sci.med gives further information on typhoid vaccine:

------------------------------------------------------------------------
From: "Mark A. Shelly" 
Subject: Re: Oral form of typhoid vaccine

>A typhoid vaccination is recommended for a trip to Costa Rica.  My family
>doctor said that the last time she gave someone a prescription for the
>vaccine they came back with an oral vaccine.  Since then she hasn't been
>able to find any information comparing the oral to the injectable form:
> - efficacy
> - scheduling (the injectable form requires 2 doses, the first a month
>   before the trip)
> - side effects (she says that the injectable form tends to make you feel
>   sick, the oral form may be an improvement).

Oral typhoid vaccine is a live but weakened (attenuated) strain (Ty21a) of
the Salmonella germ that causes typhoid fever.

The oral vaccine is probably equal to the injected vaccine in efficacy, at
about 80%.

It is given orally on an empty stomach every other day for 4 doses (total
elapsed time 6 days). It must be kept refrigerated but not frozen, a significant
limitation to use in other countries. You can't be taking antibiotics at the
same time.

It is very well tolerated. (The injected form has 80+% side effects). If you
have weakened immunity, or if you are too young to take pills, you shouldn't
use this vaccine.

I almost never recommend the injected form of typhoid vaccine. Typhoid
vaccine is recommended for travel to areas with poor water supplies when
the trip is over 3 weeks and when your eating will be "high risk".

Hope this helps

Mark Shelly
mshelly@medicine.rochester.edu
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Typhus vaccine (not available in the US) is described by Andreas Kaunzner's travel medicine Web site (http://members.aol.com/reisemed/impfung/typhus.htm). According to this site, there are two different typhus vaccines on the market in Germany. One is a live oral vaccine, which is given in three doses, and gives protection for about three years, if one stays in a region where typhus is endemic; otherwise its immunity lasts for about a year. The most common side effect, seen in fewer than 1% of those receiving the vaccine, is stomach trouble. General symptoms such as fever and chills can appear, and very seldom a rash. The other is a killed vaccine, which may be given to adults and children two years or older, and which provides immunity for at least three years. Its side effects are described as "typical side effects of vaccinations" (local reactions, fever, and allergic reactions) appearing only seldom. Kabel 1 Online has a chart of German travel vaccine recommendations (http://www.kabel1.de/reise/1998/06/26/11/) which says that typhus vaccine is given for trips of more than three months. The CDC, on the other hand, recommends hygiene and, in areas where tick typhus is endemic, tick removal and tick repellant; typhus vaccine production has been discontinued in the US.

Yellow fever is a viral infection which is spread by mosquitos. Yellow fever vaccine is a live vaccine which can be given only at certain vaccination centers. Many countries require this vaccination for entry. A booster is needed every ten years. Contraindications include egg allergy and immune deficiency. Reactions are mostly mild.

Vaccine components capable of causing adverse reactions: chick embryo components (Travel Medicine Advisor).

Travelers may also want to take anti-malarial drugs, bring insect repellant containing N,N diethylmethylbenzamide, and avoid unboiled water, raw vegetables, fruit they haven't peeled themselves, undercooked fish and shellfish, and food kept at room temperature. Other sources of travel health information are _Fielding's Travelers' Medical Companion_ and the US State Department Citizen's Emergency Center, which provides information on a variety of foreign travel risks 24 hours a day at 202-647-5225. CDC Travelers' Health Section, 404-332-4559, and Immunization Alert, 203-487-0611, have up-to-date information on vaccinations for international travel.

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Section 3n. Vaccines under development

[This section most recently updated on September 18, 1999. References include the Report of the Technical Review Group Meeting, 7-8 June 1998 WHO Global Program for Vaccines and Immunization Vaccine Research and Development (http://www.who.org/gpv-documents/DocsPDF/www9845.pdf), a New England Journal of Medicine editorial on malaria vaccine development at http://www.nejm.org/content/1997/0336/0002/0128.asp, reports on AIDS vaccine research at http://www.iapac.org/ and http://www.nih.gov/news/pr/may98/od-15a.htm, an Intellihealth report on vaccine news for 1999 (http://www.intelihealth.com/IH/ihtIH?t=18784&p=~br,IHW|~st,408|~r,WSIHW000|~b,*|), Lon Morgan's Web site on vaccine developments: http://fp1.cyberhighway.net/~lmorgan/developments/vaccine_development.htm, and National Institute of Health information on clinical trials at http://www.niaid.nih.gov/.]

Q3n.1 What vaccines are currently under development?

New vaccines under development include vaccines for HIV (vaccines are being tested both to improve the immune response in those already infected and to resist infection), respiratory syncytial virus (Rathone), malaria, leprosy, gum disease, herpes, shigella, dengue, cervical cancer, type I diabetes, and other illnesses, as well as an intranasal flu vaccine, new versions of the pneumococcal, meningococcal, and TB vaccines. Harrison's Internal Medicine has a list of vaccines in human trial, and a list of those toward which priority efforts are being targetted.

As of May, 1998, the National Institutes of Health had evaluated 23 vaccine candidates and 10 adjuvants (substances that might enhance the effect of a vaccine) in 49 Phase I and Phase II clinical trials to determine the safety of the vaccine candidates and their effect on the human immune system. These studies have been conducted with 2,900 volunteers. Despite all these vaccine candidates, the variation of retroviruses and the virus transmission directly from cell to cell by fusion pose significant obstacles. It's anyone's guess when (and if) an AIDS vaccine will be ready. Two articles which discuss AIDS vaccine development are "Vaccine Against AIDS?" in the British medical journal Lancet ((02/26/94) Vol. 343, No. 8896, P. 493) and "AIDS Vaccine: Shooting Blanks or Loaded for Bear?" in Men's Fitness ((03/94) Vol. 10, No. 3, P. 118). Information about efforts to produce an AIDS vaccine is sometimes posted in sci.med.aids, and references, updates, and current information is available by gophering to odie.niaid.nih.gov. If you have gopher, gopher odie.niaid.nih.gov will get you there. The AIDS FAQ (available from the pub/usenet/sci.med.aids directory of rtfm.mit.edu) describes some other Internet resources with information about AIDS.

When I wrote this section in 1994, I had, "The malaria vaccine has shown positive results in Phase I/II trials, which were reported on February 18, 1994 issue in the British medical journal _Vaccine_ (volume 12 no. 4, pp 328-336; 1994). (A report on an earlier trial can be found in the medical journal Lancet, volume 341, pp 705-710; l993). More details can also be found in a WHO press release kept on gopher.who.ch. The first results of Phase III trials are expected to be available in October 1994." Unfortunately, the years since then have not seen as much progress toward a malaria vaccine as was hoped. It is known to be possible to induce immunity to malaria, as letting volunteers be bit by irradiated mosquitos has done so. But translating that into an effective vaccine has proved tricky. An editorial in The New England Journal of Medicine -- January 9, 1997 -- Vol. 336, No. 2 reported that, though one vaccine has shown efficacy, recent trials in malaria endemic areas couldn't confirm that efficacy. An improved subunit vaccine reported in the same issue of NEJM, but needs to be tested in malaria endemic areas. WHO has malaria vaccine as a high priority, and aims to have an effective and affordable vaccine within the next decade.

Respiratory syncytial virus (RSV) is a major respiratory pathogen among infants and young children which results in an "estimated 90,000 hospitalizations among infants in the US every winter" (Williams, 1997). Trials have indicated that the vaccine is safe and immunogenic (produces antibodies), but there are mixed results so far on efficacy.

Shigella is one of the leading causes of diarrhoeal illnesses. A shigella vaccine is moving toward clinical trials soon.

The vaccine for periodontitis (gum disease) has shown some positive results in macaque monkeys (less bacterially induced bone loss in the vaccinated monkeys), indicating that a human periodontitis vaccine is feasiable. Full-fledged clinical trials, however, may be a decade away.

Q3n.2 What other research is being done to improve vaccines?

Research is being done to improve existing vaccines (such as the research which resulted in the new acellular pertussis vaccine). This includes efforts to decrease the number of visits, the number of doses, and the number of injections, to move immunization as early in life as possible (including research into the value of giving vaccines to pregnant women to provide protection to infants very early in life), to decrease adverse effects, to increase protection, and to increase thermal stability. One area being explored is whether it is possible to combine more vaccines in a single shot. Micro-encapsulation is an attempt to encase vaccines in microcapsules which will be released over time, mimicking repeated injections. Trans-disease vaccinology is an attempt, by genetic engineering, to create vaccines which protect against more than one disease. Efforts are also under way to produce a heat-resistant polio vaccine. (Hartveldt) (There is also a United Press International article from 3/25/94, included in the CDC AIDS Daily Summary for March 28, 1994, which discusses the effort to make a vaccine which will be effective against a variety of different viruses.)

A major vaccine safety problem is the widespread reuse of syringes in developing countries, due to scarcity, resale value, and cultural resistance to waste. In response to this problem, monodose, disposable vaccines, and solid, non-injected vaccines are being looked at. Solid vaccines would also eliminate the cost of keeping vaccines cold (a major factor in vaccine delivery costs, and reduce the cost of wasted vaccines. Other research on different vaccine delivery methods includes work on an intranasal flu vaccine and on an aerosol measles vaccine.

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Section 4. References

AAP recommendations (found at http://www.aap.org).

ACIP recommendations (found at http://www.cdc.gov/nip)

AMA Drug Evaluations Annual, 1993.

The American Medical Association Family Medical Guide. Random House, New York. 1987.

The American Hospital Formulary Service Drug Information, 1992. Published by the American Society of Hospital Pharmacists.

Boughton, Clement R. "Varicella-zoster vaccine." The Medical Journal of Australia. Vol. 159. 4 October 1993.

California Morbidity, a Biweekly Report from the Division of Communicable Disease Control, part of the State of California Health and Welfare Agency. Issues from October 31, 1987, May 21, 1993, and November 19, 1993.

Catalana, Paul, MD. "The 'Other' Childhood Immunizations." Emergency Medicine, October 15, 1992. Center for Disease Control. _Health Information for International Travel_, 1992.

Center for Disease Control Vaccine Information Statements (found at http://www.cdc.gov/nip).

Clements, C. John, Strassburg, Marc, Cutts, Felicity T. and Torel, Carol. "The epidemiology of measles." In _World Health Statistics Quarterly, Vol 45, No 2/3, 1992.

FDA. "Advisory Committee Discusses Chickenpox Vaccine." January 28, 1994. (Pulled off of fdabbs.fda.gov. Connect with login bbs to find this and other FDA information.)

Fettner, Ann Giuici. _The Science of Viruses._ Quill. William Morrow, New York, 1990.

Galazka, Artur. "Control of Pertussis in the World." In _World Health Statistics Quarterly_, Vol 45, No 2/3, 1992.

Gershon, Anna A. "Varicella - Immunization Practices in Children." Hospital Practice. Sept. 15, 1990.

Ghendon, Y. "Influenza - its impact and control." In _World Health Statistics Quarterly, Vol 45, No 2/3, 1992.

Harrison's Principles of Internal Medicine, Eleventh Edition. McGraw Hill Book Company, 1987.

Hartveldt, Frank. "The Children's Vaccine Initiative." World Health 46th year, No. 2, March-April 1993.

Historical Statistics of the United States, Colonial Times to 1970. Bicentennial Edition. US Department of Commerce, Bureau of the Census.

Hull, Harry F. and Ward, Nicholas A. "Progress towards the global eradication of poliomyelitis." In _World Health Statistics Quarterly, Vol 45, No 2/3, 1992.

Journal Watch, 9-1-93. "Infant HBV Vaccination: Doubts Remain."

Kiple, Kenneth E., Editor. _The Cambridge World History of Human Disease_.

The Lippincott Manual of Nursing Practice, Fourth Edition. 1986.

Mandell/Douglas/Bennett. Principles and Practice of Infectious Diseases, Third Edition, 1990.

The Medical Letter on Drugs and Therapeutics, Vol. 34 (Issue 875), July 24, 1992.

The Merck Manual, Sixteenth Edition. Merck Research Laboratories, 1992.

Nossal, Sir Gustav. "Prospects for new vaccines." World Health 46th year, No. 2, March-April 1993.

Onorato, Ida M., MD, Wassilak, Steven G. Md, Meade, Bruce, PhD. "Efficacy of Whole-Cell Pertussis vaccine in Preschool Children in the United States." JAMA, May 27, 1992, Vol. 267, No. 20.

Pantell, Robert H., MD, Fries, James F., MD, and Vickery, Donald M., MD. _Taking Care of Your Child: A Parents' Guide to Medical Care._ Third Edition.

The Physician's Desk Reference, 1993.

Rathone, Mobeen H., MD. "Childhood Immunizations: An Update." Infections in Medicine, June 1992.

Ryan, Frank, M.D. _The Forgotten Plague: How the Battle Against Tuberculosis Was Won - And Lost_. Little, Brown, and Company, 1993.

Shapiro, Eugene D., MD "Editorial: Pertussis Vaccines: Seeking a Better Mousetrap." JAMA, May 27, 1992, Vol. 267, No. 20.

Smith, Alice Lorraine. Principles of Microbiology. The C. V. Mosby company. St. Louis, Toronto, and London, 1992.

Statistical Abstracts of the United States, 1992.

Travel Medicine Advisor. May 1993.

Trollfors, B. and others. "A Placebo-Controlled Trial of a Pertussis-Toxoid Vaccine." NEJM, Vol 333, Number 16, October 19, 1995.

University of California, Berkeley. _The Wellness Encyclopedia._ From the editors of the UC Berkeley Wellness Letter. Houghton Mifflin Company, Boston, 1991.

Viral Hepatitis Prevention Board. Safety of hepatitis B vaccination programmes. http://esoc-www.uia.ac.be/esoc/VHPB/statement.html

Whitman, Cynthia, Belgharbi, Lahevari, Gasse, Francois, Torel, Carol, Mattei, Vittoria, and Zoffman, Henrik. "Progress towards the global elimination of poliomyelitis." In _World Health Statistics Quarterly, Vol 45, No 2/3, 1992.

WHO. The Work of WHO 1990-1991. Biennial Report of the Director General.

Wilkerson, James A., M.D. Medicine for Mountaineering, Third Edition. The Mountaineers, Seattle, Washington, 1985.

Williams, Amelia L., Ph.D. News and Perspectives: New Vaccines for Childhood Immunization. Drug Benefit Trends 9(3):10-11,15-22, 1997. (Found on Medscape.)

Wyngaarden/Smith/Bennett. Cecil Textbook of Medicine, 19th edition, 1992.

Electronic resources consulted:

American Association of Pediatrics Web site. http://www.aap.org

CDC AIDS DAILY SUMMARY (regularly posted on sci.med.aids)

CDC National Immunization Program Web site. http://www.cdc.gov/nip/

Degos, Francoise. Immunisation contre le virus de l'hépatite B : bilan de quinze années de vaccination. http://www.john-libbey-eurotext.fr/articles/aB80DA9A7/index.htm

fdabbs.fda.gov (login using name "bbs") (more recently, http://www.fda.gov)

gopher.who.ch (gopher gopher.who.ch, also:

telnet gopher.who.ch login:gopher) (more recently, http://www.who.org)

HICNet Medical News Digest (available from LISTSERV@ASUACAD.BITNET; regularly posted to sci.med)

Immunization Action Coalition Web site. http://www.immunize.org

Journal Watch Summaries (regularly posted to sci.med by jwatch@world.std.com)

Le point sur la vaccination contre l'hépatite B http://www.sante.gouv.fr/htm/pointsur/vaccins/effets_sec_hep_b.htm

Levy-Bruhl, Daniel et al. Comparaison entre les Risques de Premieres Atteintes Demyelinisantes Centrales Aigues et les Benefices de la Vaccination Contre L'Hepathite B. http://www.rnsp-sante.fr/beh/1999/9909/index.html

Medscape http://www.medscape.com

Also available on the net is the Morbidity and Mortality Weekly Report (MMWR). It is available by Worldwide Web at:

http:/www.cdc.gov/; Go to publications and scientific data, then Morbidity and Mortality Weekly Report, OR

by gopher at Duke University.

Morgan, Lon. Immunization, Vaccines, Vaccination in the Modern World http://fp1.cyberhighway.net/~lmorgan/

Swiss Medical Weekly. http://www.smw.ch

A list of Internet and Bitnet Health Sciences resources, compiled by Lee Hancock, can be ftped from the pub/nic directory of ftp.sura.net. Section 1 of the misc.kids Childhood Vaccinations FAQ
Section 2 of the misc.kids Childhood Vaccinations FAQ
Section 4 of the misc.kids Childhood Vaccinations FAQ
Back to the Childhood Vaccinations page of the Children's Health page