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.]=20

Q3f.1 What is influenza, and what are the risks of the disease?=20

Influenza has a fairly high mortality rate among the elderly and the chroni=
cally ill. Complications include pneumonia, neurological
complications, myocardia, heart block, and peripheral vasoconstriction.=20

Q3f.2 How common is influenza?=20

Outbreaks of flu occur almost every year, generally in the winter, and can =
cause thousands to be hospitalized.=20

Q3f.3 How effective is the influenza vaccine?=20

About 70-80% in young, healthy adults. About 50% effective in adults over 6=
0. (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, Numbe=
r 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 t=
he flu season when they received the flu vaccine.=20

Note that influenza vaccine protects against influenza only, and not agains=
t other respiratory infections.=20

An intranasal flu vaccine has shown efficacy in trials and may be available=
within a year.=20

Q3f.4 How long does the influenza vaccine last?=20

It has to be repeated every year, as the strains of influenza vary from yea=
r to year.=20

Q3f.5 What are some of the risks of the influenza vaccine?=20

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 condit=
ion called Guillaine-Barre syndrome. This was
many more than could normally be expected to come down with this disease (t=
hough 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.=20

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.=20

Q3f.6 When is the influenza vaccine recommended?=20

It is recommended for people who are over 65 and for people with various ch=
ronic illnesses, particularly those affecting the
lungs (including asthma) or the heart. Candidates among children include si=
milar groups to those for pneumococcal vaccine:
sickle cell, chronic renal and metabolic disease, diabetes, chronic pulmona=
ry disease, long-term aspirin therapy, and significant
cardiac disease (Catalana).=20

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).=20

The antiviral drugs amantadine and rimantadine are also effective against i=
nfluenza A, but not influenza B.=20

Q3f.7 When is the influenza vaccine contraindicated?=20

Egg allergy, hypersensitivity to thimerosal. Delay in case of an active neu=
rological 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.=20

Vaccine components capable of causing adverse reactions: chick embryo compo=
nents, formaldehyde, thimerosal (Travel
Medicine Advisor).=20

Q3f.8 Is it OK to be vaccinated for influenza during pregnancy?=20

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 t=
he risks of the vaccine (especially during the first
trimester) have to be weighed against the risks of a particular patient get=
ting the flu, and that "The clinical judgment of the
attending physician should prevail at all times in determining whether to a=
dminister the vaccine to a pregnant woman."=20

The CDC, in the October 8, 1999 issue of MMWR, recommended that "Pregnant w=
omen 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 trim=
ester 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. "=20

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Section 3g. Pneumococcal vaccine
[This section last updated September 18, 1999.]=20

Q3g.1 What is pneumococcal disease, and what are the risks of the disease?=
=20

It causes ear infections and sinusitis in children, and sometimes meningiti=
s and pneumonia.=20

Q3g.2 How common is pneumococcal disease?=20

From=20Nelson 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. =20
------------------------------------------------------------------------

There has been recent evidence of antibiotic-resistant pneumococci (see JAM=
A 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).=20

Q3g.3 How effective is the pneumococcal vaccine?=20

It protects against 23 strains of pneumococcus, 85% of those which cause ea=
r infections and almost all of those which cause
pneumonia and meningitis. Harrison's Internal Medicine estimates its effect=
iveness at 60-80%.=20

Some recent articles discussing (and debating about) the effectiveness of p=
neumococcal vaccine can be found in Arch Intern
Med 1994 Dec; 154:373, 154:2666 and 154:2531; these articles and others are=
summarized in "Featu 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 Medicin=
e 1988;108:616-625 and the New England Journal of
Medicine for 11/21/91.=20

Q3g.4 How long does the pneumococcal vaccine last?=20

According to a chart I got from Kaiser, one dose is good for life, except f=
or immune suppressed or immunodeficient patients,
who should get a booster two years later. _Travel Medicine Advisor_ also sa=
ys that no booster is required. _AHFS Drug
Information_, however, says that antibodies are elevated at least five year=
s in healthy adults, but decline to prevaccination levels
after ten years in some.=20

The reason for the apparent conflict in recommendations is that allergic re=
actions are more common after the booster shots,
but, at the same time, the booster shots are useful for maintaining immunit=
y. For this reason, there has been some debate about
the booster shots; the most recent recommendation is "revaccination with pn=
eumococcal 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 onl=
y 14-valent.=20

Journal Watch for Oct 18, 1994 summarizes an article in the Archives of Int=
ernal 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 associa=
ted 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.=20

Q3g.5 What are some of the risks of the pneumococcal vaccine?=20

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

Q3g.6 When is the pneumococcal vaccine recommended?=20

It is recommended for children 2 or older who are at increased risk of pneu=
mococcal infection. Conditions which increase risk
of pneumoccoal infection include HIV positive status, functional or anatomi=
c asplenia, and sickle cell or other
hemoglobinopathies. It is also recommended for adults 65 or older and adult=
s with significant cardiovascular or pulmonary
disorders, splenic dysfunction, asplenia, Hodgkin's Disease, multiple myelo=
ma, cirrhosis, alcoholism, renal failure, CSF leaks,
or immunosuppressive conditions.=20

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 infe=
ctions. As of 1997, four different conjugate
pneumococcal vaccines for infants were in Phase II/III trials (Williams, 19=
97)=20

Q3g.7 When is the pneumococcal vaccine contraindicated?=20

It should not be given to children under 2. It also shouldn't be given to p=
eople who have already been vaccinated (except for
booster shots for those in the highest risk categories).=20

Vaccine components capable of causing adverse reactions: phenol, polysaccha=
rides, thimerosal (Travel Medicine Advisor).=20

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Section 3h. Meningococcal vaccine [This section last updated on September 1=
8, 1999.]

Q3h.1 What is meningococcal disease, and what are the risks of the disease?=
=20

Meningococcal disease is a rare disease which causes meningitis as well as =
widespread blood infection, leading to shock and
death.=20

Q3h.2 How common is meningococcal disease?=20

About 2,500 cases a year in the US, but tens of thousands annually in sub-S=
aharan Africa.=20

Q3h.3 How effective is the meningococcal vaccine?=20

The current vaccine not highly immunogenic in children under 2, or very lon=
g lasting, and it is children under 2 who have the
highest rate of the disease. Research is being done on conjugate vaccines w=
hich would produce a greater immune response.
Global cooperation would be needed to make these affordable in developing c=
ountries. (Williams, 1997)=20

Q3h.4 How long does the meningococcal vaccine last?=20

I don't have this information.=20

Q3h.5 What are some of the risks of the meningococcal vaccine?=20

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 T=
raveller, 1992).=20

Q3h.6 When is the meningococcal vaccine recommended?=20

For children with certain types of immune disorders and during epidemic out=
breaks. 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).=20

Q3h.7 When is the meningococcal vaccine contraindicated?=20

I haven't found any, except pregnancy (when it should be given only in case=
of an outbreak).=20

Vaccine components capable of causing adverse reactions: phenol, polysaccha=
rides, thimerosal (Travel Medicine Advisor).=20

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Section 3i. Varicella (chicken pox) vaccine=20

[Note: The varicella section has been modified slightly and updated. Inform=
ation is from FDA press releases on 1/28/94 and
3/17/95 and and an article in Infectious Diseases in Children newsletter {v=
ol 8(2) February l995}. It has been further updated
based on the July 12, 1996 recommendation by ACIP. This section last update=
d on September 25, 1999. I have some
additional information on zoster which I will be merging into this section =
in my next update.]=20

Q3i.1 What is chicken pox, and what are the risks of the disease?=20

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) complication=
s include hemorrhagic varicella, encephalitis,
pneumonia, and bacterial skin infection. Possible complications in pregnanc=
y include premature birth and congenital varicella,
and mortality (of the infant, not the mother) is high. "It is estimated tha=
t there are about 9,600 chicken-pox related
hospitalizations annually, with 50 to 100 deaths." (FDA announcement, Janua=
ry 28, 1994) Another risk, unfortunately on the
increase, is invasive group A streptococcal infections, to which children i=
ll with varicella may be susceptible.=20

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 defe=
cts ranging from "multisystem involvement to limb
hypoplasia and skin scars." There were no cases of congenital varicella syn=
drome among infants whose mothers had varicella
after 20 weeks or among those whose mothers received anti-varicella-zoster =
immunoglobulin after they were exposed.=20

Q3i.2 How common is chicken pox?=20

An estimated 3.7 million Americans are affected by chickenpox each year, wi=
th more than 90% of the cases occurring in
persons under 15 years of age. 33% of cases are estimated to occur in child=
ren ages 1 to 4, and 44% in children ages 5 to 9
(estimates from January 28, 1994 FDA announcement).=20

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).=20

I do not have data on how varicella incidence has been affected by the avai=
lability of the vaccine, but vaccine coverage is still
(as of 1999) fairly low for this particular vaccine.=20

Q3i.3 What is Herpes Zoster?=20

Following chickenpox infection, the varicella zoster virus persists in a la=
tent form in sensory nerve ganglia without any signs of
illness. The virus can be reactivated causing herpes zoster or shingles, wh=
ich is a painful small blister-like rash in the distribution
of one or more sensory nerve roots. It is estimated that 15% of the populat=
ion 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 episode=
s. 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.=20

(Information on the effect of the vaccine on herpes zoster will be added to=
this FAQ later.)=20

Q3i.4 What is the current recommendation for the chicken pox vaccine be par=
t for children?=20

The chickenpox (varicella) vaccine was first licensed for use among high-ri=
sk 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 reco=
mmends that all children be routinely
vaccinated at 12-18 months of age. The American Academy of Pediatrics recom=
mends that it be given to everyone over the
age of one who is not already immune to chicken pox. Currently it is approv=
ed by the FDA for a single injection in children
ages 12 months to 12 years, and two injections 4-8 weeks apart for adolesce=
nts 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 eithe=
r at the 12 or 15 month checkup. Research is underway
for development of a combination measles, mumps, rubella and varicella vacc=
ine to avoid the need for a second injection. It is
unknown when this product may become licensed.=20

Q3i.5 What is the current recommendation for adults?=20

************************************************** ***********************
[Contributed shortly before the vaccine was licensed.]
From=20J Thompson ):

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 im=
mune status, and that those who are not immune
be vaccinated. Priority should be given to vaccinating those at highest ris=
k for exposure and for transmitting the disease. There
is an antibody titre which can be done on adults who are not sure whether t=
hey are immune to chicken pox.=20

Q3i.6 How effective is the chicken pox vaccine?=20

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 a=
ll of the vaccinated patients who got chickenpox had
a milder form of the disease.=20

Q3i.7 How long does the chicken pox vaccine last?=20

We don't know yet. It is estimated to last at least six years. (Lancet, Apr=
il 16, 1994) "Children immunized as long as six years
earlier continued to be well protected. . . . So far, the US data show pers=
istence of antibodies for three to four years after
immunization; data from Japan show persistence of antibodies for seven to 1=
0 years in healthy children." (Gershon)=20

Q3i.8 What reactions have been reported following the chickenpox vaccine?=
=20

Adverse reactions reported were mild and included redness, hardness and swe=
lling at the injection site, fatigue, malaise and
nausea. The vaccine has been used in Japan routinely for more than 10 years=
with no complications.=20

Q3i.9 Will a second dose be necessary in younger children?=20

The question of a "booster" dose remains uncertain at this point. The manuf=
acturer has agreed to perform postmarketing studies
to determine the long-term effects of the vaccine and whether there is a ne=
ed for a booster immunization.=20

Q3i.10 For which groups is the chicken pox vaccine especially recommended?=
=20

People with HIV, nephrosis, severe asthma, and similar chronic diseases, bu=
t especially leukemia. Conditions for vaccination of
leukemic children a remission for at least a year, off maintenance thera=
py for a week before and a week after getting the
vaccine, and cellular immunity intact. (Catalana)=20

Q3i.11 When is the chicken pox vaccine contraindicated?=20

************************************************** ***********************
From=20the April 1995 issue of Medical Sciences Bulletin, published by=20
Pharmaceutical Information Associates ) and=20
available by Email subscription as MSB-L.

Use of Varivax is contraindicated for patients who are hypersensitive to an=
y
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 gr=
oups, 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 substan=
tiated or confirmed by a laboratory). Pregnant
women should not be vaccinated, as the effect on the fetus is unknown.=20

Although no adverse reactions from taking aspirin after the vaccine have be=
en reported, it is recommended that people
receiving the varicella vaccine refrain from taking aspirin for 6 weeks aft=
erwards, because of the association between aspirin
and Reyes syndrome following varicella.=20

Q3i.12 Is there a gamma globulin for chicken pox?=20

Yes, but it is only available to people at especially high risk from chicke=
n 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 p=
ox, but aren't otherwise at high risk from
exposure. The varicella immune globulin isn't likely to be available to the=
se 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.=20

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Section 3j. BCG (tuberculosis) vaccine
[This section last updated on September 25, 1999, based on the ACIP recomme=
ndation which was published in MMWR on
April 26, 1996, and which can be found at ftp://ftp.cdc.gov/pub/Publication=
s/mmwr/rr/rr4504.pdf]=20

Q3j.1 What is tuberculosis, and what are the risks of the disease?=20

Tuberculosis is a chronic bacterial infection that is spread by inhaling dr=
oplets 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.=20

Q3j.2 How common is tuberculosis?=20

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 19=
70, 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 are=
as. A Morbidity and Mortality Weekly Report
article summarized in the June 15, 1994 HICN726 Medical News gives the inci=
dence 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%.=20

A joint statement by ACIP and the Advisory Council for the Elimination of T=
uberculosis, published in MMWR, Volume 45,
No. RR-4, April 26, 1996 states that the incidence of TB declined through 1=
984, increased from 1985 through 1992, and
declined slightly in 1993 and 1994. 57% of the total number of TB cases wer=
e reported in five states: California, New York,
Florida, Illinois, and Texas. Overall incidence rates are twice as high for=
men as for women.=20

Q3j.3 How effective is the BCG vaccine?=20

The AHFS Drug Information, 1992 says that its effectiveness is unknown, "Di=
agnostic and clinical evidence has generally
demonstrated a reduction` in the incidence of tuberculosis." Tuberculin sen=
sitivity is highly variable, depending on the strain, and
the relationship between tuberculin sensitivity and immunity has not been a=
dequately studied.=20

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

A New York Times article ("Tuberculosis Vaccine Found Surprisingly Effectiv=
e in Studies", New York Times, 03/02/94, P.
C14), recently reported that "A new statistical study by the Centers for Di=
sease 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.=20

The joint ACIP and ACET report in the April 26, 1996 MMWR says that there a=
re 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 diffe=
rent BCG strains have ranged from 0% to 80%. Two
recent meta-analyses of the published literature have attempted to calculat=
e summary estimates of efficacy. The first analyzed
data from 10 randomized clinical trials and 8 case-control studies since 19=
50. It estimated protective efficacy against meningeal
and miliary TB in children in clinical trials as 88%, and the efficacy in c=
ase-control studies as 75%. There was too much
variability in data on efficacy against pulmonary TB for them to come up wi=
th 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 adult=
s.=20

Q3j.4 How long does the BCG vaccine last?=20

It is of limited duration (Ryan). _AHFS Drug Information_ says that several=
studies showed tuberculin sensitivity lasting 7-10
years.=20

Q3j.5 What are some of the risks of the BCG vaccine?=20

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 BC=
G 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 v=
accinees, in Sweden and Finland, respectively.
Reactions may be more frequent among people with symptomatic HIV infection.=
=20

************************************************** ***********************
From=20J Thompson ):

The main strategy of TB control in the US is monitoring those at risk o=
f
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 wil=
l
exhibit redness and swelling at the site of the PPD injection (the criterio=
n
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?=20

BCG vaccine is given in developing countries because it is easy to administ=
er, inexpensive, and rarely has serious side effects.
Some industrialized countries (e.g. Great Britain, France, Scandinavia) hav=
e also used it, for vaccination of children in general
and of household contacts of people with TB. Others (e.g. the US, the Nethe=
rlands) have not.=20

Because of the low rate of new infections, the availability of low-cost iso=
niazid prophylaxis for people who are exposed, and
the availability of effective treatment which quickly make patients non-con=
tagious and cures them, the BCG vaccine hasn't been
considered necessary in the US. There might be some changes in these recomm=
endations 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 medic=
ation and thus increasing patient compliance (antibiotic
treatment which is discontinued too early increases the development of drug=
resistant TB strains).=20

In the US, the AAP, ACIP, and the American Thoracic Society recommend BCG f=
or 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 fo=
r whom the usual surveillance and treatment
programs have failed or are not feasible." (_AHFS Drug Information_) ACIP a=
lso recommends vaccination for children who
are continually exposed to a patient who is infected with a strain of TB wh=
ich is resistant to isoniazid and rifampin (MMWR,
April 26, 1996). It is recommended for travel only for people who will be i=
n 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.=20

BCG also has some use against certain tumors (in particular, bladder cancer=
).=20

************************************************** ***********************
From=20J Thompson ):

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?=20

Hypersensitivity to the vaccine, positive TB skin test, recent smallpox vac=
cination, 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 as=
sociated wtih BCG vaccination, its use is not
recommended during pregnancy.=20

Vaccine components capable of causing adverse reactions: Triton WR 1339 (Tr=
avel Medicine Advisor).=20

Q3j.8 What are some other methods of controlling tuberculosis?=20

Tuberculin skin screening and use of drugs such as isoniazid. Pasteurizatio=
n of milk and testing of cows for tuberculosis are also
useful.=20

=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3 D=3D=3D=3D=3D=3D=3D=3D=3D=
=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3 D=3D=3D=3D=3D=3D=3D=3D=3D=
=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3 D=3D=3D=3D=3D=3D=3D=3D=3D=
=3D=3D=3D=3D
Section 3k. Hepatitis A=20

[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 sect=
ion last updated September 19, 1999.]=20

Q3k.1 What is hepatitis A and what are the risks of the disease?=20

There are several forms of hepatitis (infection of the liver) which cause j=
aundice, nausea and weakness. Hepatitis A is caused
by infection with hepatitis A virus (HAV) which is acquired primarily throu=
gh 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 acco=
mpanied by jaundice. Among older children and adults,
the illness is usually symptomatic, and jaundice occurs in 70% of cases. S=
ymptoms usually last for 2 months, but 10-15% of
people infected have illness or relapses for up to 6 months. 11-22% of peop=
le who have hepatitis A are hospitalized, and
hepatitis A is responsible for an estimated 100 deaths a year (these number=
s from the ACIP recommendation on hepatitis A -
the AAP recommendation gives similar, but not identical, numbers).=20

Hepatitis A should not be confused with hepatitis B, which is less contagio=
us 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.=20

Some sources of general information on hepatitis can be found in the hepati=
tis B section of this FAQ.=20

Q3k.2 How common is hepatitis A?=20

During the past several decades, the incidence of hepatitis A in the U.S. h=
as 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 hig=
her, 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 19=
88-1991 (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 av=
oiding contaminated food and drink, but many
travelers succumb to temptation, assume food at hotels is safe, buy from st=
reet 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)=20

Q3k.3 Who is at risk for acquiring hepatitis A?=20

International travelers and individuals residing in hepatitis A endemic are=
as are at risk for acquiring disease. Other risk groups
include homosexual men, injecting drug users, hemophilic patients, veterina=
ry workers and certain research occupations
working with infected animals (particularly people working with non-human p=
rimates). Workers at day care centers, institutions
for the developmentally disabled, food service establishments and healthcar=
e settings are also at some increased risk.=20

Q3k.4 Is there a vaccine to protect against hepatitis A?=20

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 America=
n Academy of Pediatrics also published
a policy statement in December 1996. The vaccine has been in use in Europe =
since 1992.=20

Q3k.5 How is it to be administered?=20

According to the labeling, the vaccine is given in a two-dose schedule to a=
dults 18 years of age and older, the second dose
being given 6-12 months after the first. Children and adolescents 2-18 year=
s 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 a=
dministered by intramuscular injection in the deltoid
(upper arm), and can be given with other vaccines without loss of immunogen=
icity.=20

Q3k.6 How effective is the vaccine?=20

A single dose of the vaccine induced antibodies in 88% to 96% of subjects b=
y two weeks and in 97% to 100% by one month.
Completion of the full vaccine schedule is recommended to ensure high antib=
ody levels and long-term protection. Efficacy trials
in children and adolescents show it is 94% (or more) effective against ende=
mic hepatitis A virus.=20

According to the AAP recommendation for hepatitis A, on December, 1996: "Cl=
inical studies suggested a possible
herd-immunity effect if more than 80% of the estimated susceptible individu=
als were vaccinated. A single dose of Havrix in
Alaskan native villages with endemic HAV disease resulted in a dramatic dec=
rease in cases within 8 weeks of vaccination. A
similar abrupt decrease in HAV cases was observed after two doses of vaccin=
e 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 p=
rotective efficacy was 100%. "=20

Q3k.7 How long does immunity last?=20

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 mo=
dels of antibody decline suggest that the
protective levels of anti-HAV could persist for at least 20 years.=20

Q3k.8 What are some of the risks of the vaccine?=20

Information on adverse events comes from prelicensure clinical studies worl=
dwide 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, th=
ere is a severe allergic reaction within a few minutes to
a few hours of the shot.=20

Q3k.9 When is hepatitis A vaccine contraindicated?=20

The vaccine should not be administered to persons with a history of hyperse=
nsitivity 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 pregnan=
cy. People mildly ill at the time of vaccination may
get the vaccine, but people moderately to severely ill should wait until th=
ey recover.=20

Q3k.10 What groups at risk are be included in a recommendation to receive h=
epatitis A vaccination?=20

ACIP recommends the vaccine for:=20

1. Persons 2 years of age or older traveling or working in countries with h=
igh or intermediate endemicity of infection. The
vaccine series should be started at least one month before travelling.=20

2. Persons living in communities with high rates of HAV infection; for exam=
ple, American Indian, Alaska Native, Pacific
Islander, and some religious communities.=20

3. Men who have sex with men.=20

4. People who use street drugs (injected or non-injected).=20

5. People who work with hepatitis A infected primates or with hepatitis A i=
n a research setting should be vaccinated. No other
groups have been shown to be at increased risk for hepatitis A due to occup=
ational exposure.=20

6. Persons with chronic liver disease.=20

7. Persons who use clotting factor concentrates.=20

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 t=
o be cost effective.=20

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, hospita=
l personnel, food handlers, and people with hemophilia.=20

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 t=
he national average). These states a Arizona,
Alaska, California, Idaho, Nevada, New Mexico, Oklahoma, Oregon, South Dako=
ta, Utah and Washington.=20

Any healthy individual 2 years of older may receive hepatitis A vaccine at =
the discretion of the physician and patient or parent.=20

Q3k.11 Is it possible that hepatitis A vaccine (like hepatitis B vaccine) m=
ight eventually be recommended for routine
administration to children and adults?=20

Those in public health say that control of hepatitis A infection will be fa=
cilitated by the development of vaccines that combine
hepatitis A with other routine childhood immunizations. The CDC's draft sta=
tement notes the important role of children in
hepatitis A transmission, and that "it is likely that routine childhood vac=
cination will be the only way to significantly decrease
hepatitis A rates in the U.S."=20

=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3 D=3D=3D=3D=3D=3D=3D=3D=3D=
=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3 D=3D=3D=3D=3D=3D=3D=3D=3D=
=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3 D=3D=3D=3D=3D=3D=3D=3D=3D=
=3D=3D=3D=3D
Section 3l Rotavirus vaccine
[This section last updated on October 23, 1999.]=20

Q3l.1 What is rotavirus, and what are the risks of the disease?=20

Rotavirus is one of the major causes of gastroenteritis among infants and s=
mall children in most countries. Symptoms are fever,
vomiting, diarrhea, and dehydration, with vomiting and dehydration more com=
mon than with other diarrheas. The illness
normally lasts 3-9 days, and becomes chronic only in immunodeficient childr=
en.=20

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 fr=
equent, and is epidemic only in China. In tropical
climates, rotavirus infection occurs year round, while in temperate climate=
s it is seasonal. Rotavirus can survive for hours on
human hands and for days on inanimate surfaces, and resists common disinfec=
tants.=20

Rehydration therapy makes death infrequent in developed countries. On the o=
ther hand, it is one of the most common causes of
hospitalization among infants during the winter months. Cecil Textbook of M=
edicine estimates that it is responsible for 35-52%
of the cases acute diarrheal illness needing hospitalization in infants and=
young children, in US.=20

Q3l.2 How common is rotavirus?=20

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

Q3l.3 What is the current status of the rotavirus vaccine?=20

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=20

A brief history of the release and withdrawal of this vaccine follows.=20

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 v=
accine 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 Committ=
ee 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.=
=20

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 i=
nvestigate 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 thes=
e adverse reactions, before a decision needed to be
made about whether the vaccine should be used prior to this year's rotaviru=
s season. Results of a case-control study were
expected to be available by October, 1999. Additional studies could continu=
e 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.=20

Q3l.4 How effective is the rotavirus vaccine?=20

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.=20

The rotavirus vaccine doesn't confer full immunity, but protects against se=
vere 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:=20

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.=20

Trial 2: 9% of infants in placebo group saw a doctor for diarrhea and vomit=
ing, compared with 2% in vaccine group. None in
the vaccine group needed hospitalization.=20

Both trials were by the manufacturer, and not published in the medical lite=
rature at the time of approval.=20

A third trial, in Finland, showed similar results.=20

Q3l.5 Is the rotavirus vaccine effective for breastfeeding infants?=20

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.=20

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 infan=
ts.=20

Q3l.6 How long does the rotavirus vaccine last?=20

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.=20

Efficacy persisted for two years in US and Finnish trials. Since followup h=
as only been done for two years, it is not known
whether efficacy persists beyond that time.=20

Q3l.7 What is intussusception?=20

Intussusception is a bowel obstruction in which one segment of the bowel be=
comes enfolded within another segment.=20

Q3l.8 What is the relationship between the rotavirus vaccine and intussusce=
ption?=20

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.=20

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 obtain=
ed from the manufacturer.=20

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 surgica=
l reduction. All recovered. 14 were spontaneous
reports, and one was obtained through active postlicensure surveillance. Ac=
cording to the report, "The manufacturer had
distributed approximately 1.8 million doses of RRV-TV as of June 1, 1999, a=
nd estimated that 1.5 million doses (83%) had
been administered. Given this information, 14-16 intussusception cases amon=
g infants would be expected by chance alone
during the week following receipt of any dose of RRV-TV.=20

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 in=
tussusception.=20

A further announcement by the FDA, made on September 14, 1999, reported tha=
t 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.=20

Further study is being done.=20

Q3l.9 Why was a connection between the rotavirus vaccine and intussusceptio=
n not observed prior to FDA approval of the
vaccine?=20

Approval by the FDA only requires trials on about 5,000-10,000 subjects. Ra=
re reactions to a new drug or vaccine will
therefore be unknown at the time of FDA approval.=20

Q3l.10 What other reactions have been reported following the rotavirus vacc=
ine?=20

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.=20

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 administr=
ation to older children are not available.=20

Irritability, decreased appetite, and decreased activity, were reported mor=
e often than with the placebo for five days. Diarrhea
was not reported more often than with the placebo.=20

Q3l.11 Can the rotavirus vaccine be effectively used in developing countrie=
s?=20

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).=20

Q3l.12 When is the rotavirus vaccine contraindicated?=20

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.=20

The rotavirus vaccine should not be given in case of: Infants with hypersen=
sitivity to aminoglycoside antibiotics, amphotericin B,
or monosodium glutamate that are components of the vaccine, or an anaphylac=
tic reaction to a previous dose of the rotavirus
vaccine.=20

Until further data are available, this live-attenuated vaccine should not b=
e given to children who are immunosuppressed or
immunodeficient. Babies of women who are HIV-infected should not get the va=
ccine unless these babies have tested as
HIV-negative at the age of two months or older.=20

The rotavirus vaccine should be postponed in case of: Acute vomiting and di=
arrhea (efficacy is uncertain in this case).
Moderate or severe fever.=20

The rotavirus vaccine may be given in case of: Breastfeeding, premature bir=
th, 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 immunoc=
ompromised may be immunized.=20

=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3 D=3D=3D=3D=3D=3D=3D=3D=3D=
=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3 D=3D=3D=3D=3D=3D=3D=3D=3D=
=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3 D=3D=3D=3D=3D=3D=3D=3D=3D=
=3D=3D=3D=3D
Section 3m. Other vaccines which are available
[This section last updated September 17, 1999.]=20

Q3m.1 What other vaccines are available and when are they given?=20

Other vaccines available include vaccines for cholera, Japanese encephaliti=
s, 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 availabl=
e for a variety of diseases.=20

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_, w=
hich 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 som=
e 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 c=
alled _INTERNATIONAL TRAVEL AND
HEALTH: Vaccination Requirements and Health Advice_, and copies may be orde=
red from WHO Distribution and Sales,
CH-1211, Geneva 27, telephone (41 22) 791 2476; fax (41 22) 788 0401. The p=
rice is 15 Swiss Francs; in developing
countries: 10.50 Swiss Francs. Further information about rabies can be foun=
d 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.=20

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 veterinaria=
ns and lab workers. Since vaccines given by the
military to soldiers are outside the scope of a FAQ primarily concerned wit=
h vaccines which might be given to children, I will
not be discussing the anthrax vaccine further.=20

Cholera is an intestinal infection spread by contaminated food and water. C=
holera vaccination is about 25-50% effective in
reducing clinical illness for 3-6 months after vaccination (with the greate=
st protection during the first two months). (_Health
Information for Travellers_ gives the effectiveness as 50%, and AHFS Drug I=
nformation gives it as 25-50%.) Boosters are
every six months for travelers who will be staying for a long time in chole=
ra-endemic areas. Serious reactions are rare. Since
the effectiveness is so low, neither the CDC nor the WHO actually recommend=
s the vaccine, but some countries require it.
According to AHFS Drug Information, "_Cholera vaccine does not prevent tran=
smission of infection_, and should not be used
to manage contacts of imported cholera cases or to control the spread of in=
fection."=20

Vaccine components capable of causing adverse reactions: bacterial componen=
ts (Travel Medicine Advisor). The vaccine
should not be given to children under 6 months.=20

Japanese encephalitis B vaccine, licensed in 1993, is given to travelers "w=
ho 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 thi=
s vaccine should be observed for ten days.=20

Lyme disease vaccine, licensed on December 21, 1998, is licensed (as of Sep=
tember, 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 usin=
g 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, th=
e 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.=20

It is unlikely that your child will ever need a plague vaccination. The dis=
ease is found among rural rodents in some areas,
including the Western third of the US, but urban outbreaks are now rare. Va=
ccination is only recommended for people at
increased risk due to research or field activities in epizootic areas. An a=
lternative for people at increased risk is tetracycline
prophylaxis. _AHFS Drug Information_ gives the vaccine's effectiveness as 9=
0% 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.=20

Vaccine components capable of causing adverse reactions: phenol, beef prote=
in, soya, casein (Travel Medicine Advisor).=20

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 inc=
rease 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, includin=
g 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 co=
rnea transplants from people who had died of
undiagnosed (before the transplant) cases of rabies. The chance of infectio=
n 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.=20

In case of exposure to rabies, the wound should be immediately and thorough=
ly 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 glob=
ulin if the person has not been previously
vaccinated), as the disease is, for all practical purposes, always fatal on=
ce rabies symptoms begin to show up. (A few people
have recently survived after symptoms appeared, but they all had serious br=
ain damage.) Pre-exposure vaccination is given to
people who live in or visit rabies endemic areas and to people whose profes=
sions or activities put them at extra risk, such as lab
workers, veterinarians, and spelunkers. The highest travel risk is where do=
g rabies is still endemic.=20

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 r=
anges 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 va=
ccine, while previously vaccinated people get
rabies vaccine alone, in a smaller amount. Adverse effects include local re=
actions (30-74% of vaccinees) and mild systemic
reactions (e.g. headache, nausea, 5-40% of vaccinees). About 6% of vaccinee=
s 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.=20

Vaccine components capable of causing adverse reactions: neomycin, phenol r=
ed, thimerosal (Travel Medicine Advisor).=20

The following posting from sci.med, by Achim Lohse, provides further inform=
ation about rabies vaccine (the side effect under
discussion is anaphylactic shock):=20

----------------------------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 complet=
e
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 officia=
l
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 possib=
le
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 contac=
t
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 exposu=
re
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


------------------------------------------------------------------------

From: Achim Lohse=20
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 ar=
ea.

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 ti=
tre
(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 highes=
t
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 testi=
ng
is done by the _Ontario_ Provincial Laboratory, so it's a slow and costly
undertaking.

regards,

Achim



------------------------------------------------------------------------

Smallpox vaccine is no longer given, because smallpox has been eliminated b=
y 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 m=
ajor 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 t=
hat 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 un=
der quarantine). (Kiple) The only people who still
need to be vaccinated for smallpox are the people who work in the labs wher=
e the virus is kept.=20

Vaccine components capable of causing adverse reactions: polymyxin B, strep=
tomycin, chlortetracycline, neomycin, phenol,
brilliant green dye, glycerin (Travel Medicine Advisor).=20

Typhoid is spread by contaminated food and water. The vaccine protects 70-9=
0% of recipients. There are two forms of the
vaccine: oral (live), and parenteral (killed). The oral vaccine shouldn't b=
e given to immune-compromised people. Otherwise,
there are few adverse reactions, mostly local discomfort and sometimes feve=
r and malaise. Boosters are every three years for
parenteral and five years for oral vaccine.=20

Vaccine components capable of causing adverse reactions: phenol, bacterial =
components (Travel Medicine Advisor).=20

The following posting from sci.med gives further information on typhoid vac=
cine:=20

------------------------------------------------------------------------
From: "Mark A. Shelly"=20
Subject: 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 signif=
icant
limitation to use in other countries. You can't be taking antibiotics at th=
e
same time.

It is very well tolerated. (The injected form has 80+% side effects). If yo=
u
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

------------------------------------------------------------------------

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 sit=
e, there are two different typhus vaccines on the
market in Germany. One is a live oral vaccine, which is given in three dose=
s, 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 s=
ymptoms such as fever and chills can appear, and
very seldom a rash. The other is a killed vaccine, which may be given to ad=
ults 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.=20

Yellow fever is a viral infection which is spread by mosquitos. Yellow feve=
r vaccine is a live vaccine which can be given only at
certain vaccination centers. Many countries require this vaccination for en=
try. A booster is needed every ten years.
Contraindications include egg allergy and immune deficiency. Reactions are =
mostly mild.=20

Vaccine components capable of causing adverse reactions: chick embryo compo=
nents (Travel Medicine Advisor).=20

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, under=
cooked fish and shellfish, and food kept at room
temperature. Other sources of travel health information are _Fielding's Tra=
velers' Medical Companion_ and the US State
Department Citizen's Emergency Center, which provides information on a vari=
ety 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.=20

=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3 D=3D=3D=3D=3D=3D=3D=3D=3D=
=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3 D=3D=3D=3D=3D=3D=3D=3D=3D=
=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3 D=3D=3D=3D=3D=3D=3D=3D=3D=
=3D=3D=3D=3D
Section 3n. Vaccines under development=20

[This section most recently updated on September 18, 1999. References inclu=
de the Report of the Technical Review Group
Meeting, 7-8 June 1998 WHO Global Program for Vaccines and Immunization Vac=
cine Research and Development
(http://www.who.org/gpv-documents/DocsPDF/www9845.pdf), a New England Journ=
al 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 I=
ntellihealth report on vaccine news for 1999
(http://www.intelihealth.com/IH/ihtIH?t=3D18784&p=3D~br,IHW|~st,408|~r,WSIH=
W000|~b,*|), Lon Morgan's Web site on
vaccine developments: http://fp1.cyberhighway.net/~lmorgan/developments/vac=
cine_development.htm, and National Institute of
Health information on clinical trials at http://www.niaid.nih.gov/.]=20

Q3n.1 What vaccines are currently under development?=20

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 viru=
s (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.=20

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 conduc=
ted with 2,900 volunteers. Despite all these
vaccine candidates, the variation of retroviruses and the virus transmissio=
n 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 Lanc=
et ((02/26/94) Vol. 343, No. 8896, P. 493) and
"AIDS Vaccine: Shooting Blanks or Loaded for Bear?" in Men's Fitness ((03/9=
4) 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 od=
ie.niaid.nih.gov will get you there. The AIDS FAQ
(available from the pub/usenet/sci.med.aids directory of rtfm.mit.edu) desc=
ribes some other Internet resources with information
about AIDS.=20

When I wrote this section in 1994, I had, "The malaria vaccine has shown po=
sitive 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, volu=
me 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 Ph=
ase III trials are expected to be available in
October 1994." Unfortunately, the years since then have not seen as much pr=
ogress toward a malaria vaccine as was hoped. It
is known to be possible to induce immunity to malaria, as letting volunteer=
s 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 efficac=
y, recent trials in malaria endemic areas couldn't
confirm that efficacy. An improved subunit vaccine reported in the same iss=
ue 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.=20

Respiratory syncytial virus (RSV) is a major respiratory pathogen among inf=
ants and young children which results in an
"estimated 90,000 hospitalizations among infants in the US every winter" (W=
illiams, 1997). Trials have indicated that the
vaccine is safe and immunogenic (produces antibodies), but there are mixed =
results so far on efficacy.=20

Shigella is one of the leading causes of diarrhoeal illnesses. A shigella v=
accine is moving toward clinical trials soon.=20

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.=20

Q3n.2 What other research is being done to improve vaccines?=20

Research is being done to improve existing vaccines (such as the research w=
hich resulted in the new acellular pertussis
vaccine). This includes efforts to decrease the number of visits, the numbe=
r of doses, and the number of injections, to move
immunization as early in life as possible (including research into the valu=
e 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, mimickin=
g repeated injections. Trans-disease vaccinology is
an attempt, by genetic engineering, to create vaccines which protect agains=
t more than one disease. Efforts are also under way
to produce a heat-resistant polio vaccine. (Hartveldt) (There is also a Uni=
ted Press International article from 3/25/94, included
in the CDC AIDS Daily Summary for March 28, 1994, which discusses the effor=
t to make a vaccine which will be effective
against a variety of different viruses.)=20

A major vaccine safety problem is the widespread reuse of syringes in devel=
oping countries, due to scarcity, resale value, and
cultural resistance to waste. In response to this problem, monodose, dispos=
able vaccines, and solid, non-injected vaccines are
being looked at. Solid vaccines would also eliminate the cost of keeping va=
ccines 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.=20

=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3 D=3D=3D=3D=3D=3D=3D=3D=3D=
=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3 D=3D=3D=3D=3D=3D=3D=3D=3D=
=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3D=3 D=3D=3D=3D=3D=3D=3D=3D=3D=
=3D=3D=3D=3D
Section 4. References=20

AAP recommendations (found at http://www.aap.org).=20

ACIP recommendations (found at http://www.cdc.gov/nip)=20

AMA Drug Evaluations Annual, 1993.=20

The American Medical Association Family Medical Guide. Random House, New Yo=
rk. 1987.=20

The American Hospital Formulary Service Drug Information, 1992. Published b=
y the American Society of Hospital
Pharmacists.=20

Boughton, Clement R. "Varicella-zoster vaccine." The Medical Journal of Aus=
tralia. Vol. 159. 4 October 1993.=20

California Morbidity, a Biweekly Report from the Division of Communicable D=
isease Control, part of the State of California
Health and Welfare Agency. Issues from October 31, 1987, May 21, 1993, and =
November 19, 1993.=20

Catalana, Paul, MD. "The 'Other' Childhood Immunizations." Emergency Medici=
ne, October 15, 1992. Center for Disease
Control. _Health Information for International Travel_, 1992.=20

Center for Disease Control Vaccine Information Statements (found at http://=
www.cdc.gov/nip).=20

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.=20

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.)=20

Fettner, Ann Giuici. _The Science of Viruses._ Quill. William Morrow, New Y=
ork, 1990.=20

Galazka, Artur. "Control of Pertussis in the World." In _World Health Stati=
stics Quarterly_, Vol 45, No 2/3, 1992.=20

Gershon, Anna A. "Varicella - Immunization Practices in Children." Hospital=
Practice. Sept. 15, 1990.=20

Ghendon, Y. "Influenza - its impact and control." In _World Health Statisti=
cs Quarterly, Vol 45, No 2/3, 1992.=20

Harrison's Principles of Internal Medicine, Eleventh Edition. McGraw Hill B=
ook Company, 1987.=20

Hartveldt, Frank. "The Children's Vaccine Initiative." World Health 46th ye=
ar, No. 2, March-April 1993.=20

Historical Statistics of the United States, Colonial Times to 1970. Bicente=
nnial Edition. US Department of Commerce, Bureau
of the Census.=20

Hull, Harry F. and Ward, Nicholas A. "Progress towards the global eradicati=
on of poliomyelitis." In _World Health Statistics
Quarterly, Vol 45, No 2/3, 1992.=20

Journal Watch, 9-1-93. "Infant HBV Vaccination: Doubts Remain."=20

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