Archive-name: misc-kids/vaccinations/part3
Posting-Frequency: monthly
Last-Modified: February 11, 1996

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Section 3f. Influenza

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.

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 1976-9177.  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."

===============================================================================
Section 3g. Pneumococcal vaccine

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.

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).

===============================================================================
Section 3h. Meningococcal vaccine

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.

Q3h.3	How effective is the meningococcal vaccine?

I don't have this information.

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).

===============================================================================
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}.  This section will be further modified when
ACIP comes out with its statement.]

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)

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).

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.

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

Q3i.4   When will the chicken pox vaccine be available?

The chickenpox (varicella) vaccine was licensed by FDA on March
17, l995.  It is manufactured by Merck and Co. Inc. under the
trade name "Varivax."  Health care providers are expected to
receive vaccine within 8 weeks of the licensure date.

Q3i.5   Will the chicken pox vaccine be part of the regular
schedule of vaccinations?

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 show 
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.6	Will adults be able to get the chicken pox vaccine?

*************************************************************************
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.
*************************************************************************

There is an antibody titre which can be done on adults who are not sure
whether they are immune to chicken pox.

Q3i.7	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.8	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.9  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.10  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.11	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.12	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.
*************************************************************************

Q3i.13	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.

===============================================================================
Section 3j. BCG (tuberculosis) vaccine

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%.

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.

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.)

*************************************************************************
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_)  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.

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 currently (as of April
l995) under consideration by the ACIP.

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 offen 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.

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
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.

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.  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.  A draft ACIP
recommendation on hepatitis A vaccine usage should be finalized and
published by July.  The American Academy of Pediatrics will also be
publishing recommendations in the near future.  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?
 
Efficacy trials in children and adolescents show it is 94% (or
more) effective against endemic hepatitis A virus.

Q3k.7	How long does immunity last?

Firm data on long-term protection are limited because the vaccine
has been under investigation for only 4 years.  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
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.

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.

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

The ACIP draft recommendation currently under review includes the
following:

1. Persons traveling or working in countries with high or
intermediate endemicity of infection

2. Persons living in communities with high rates of HAV infection
and periodic HAV outbreaks.

3. Homosexual men

4. Intravenous drug users

5. Persons with occupational risk of infection (e.g., persons who
work with experimentally HAV-infected non-human primates or with
HAV in a laboratory setting).  Other occupational groups such as
health care workers, sewerage workers, persons working in day care
settings or foodhandlers have not been shown to be at significantly
increased risk to warrant this recommendation.

6. Persons with chronic liver disease.
 
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. Other vaccines which are available

Q3l.1	What other vaccines are available and when are they given?

Other vaccines available include vaccines for cholera, Japanese
encephalitis, typhoid, yellow fever, rabies, and plague.  _Travel Medicine
Advisor_ also mentions a vaccine for typhus; I haven't collected
information on this yet.  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. 

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 shoudl 
be observed for ten days.

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 <LOHSEACH@UREGINA1>
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" <mshelly@troi.cc.rochester.edu>
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
------------------------------------------------------------------------

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.

===============================================================================
Section 3m. Vaccines under development

Q3m.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), rotavirus, and respiratory syncytial virus
(Rathone), malaria, leprosy, gum disease, Lyme disease, herpes and other
illnesses.  Harrison's Internal Medicine has a list of vaccines in human
trial, and a list of those toward which priority efforts are being
targetted. 

While at least 15 candidate vaccines are being developed for AIDS,
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.  

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.  

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.

Q3m.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.)

===============================================================================
Section 4. References

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.

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.

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.

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.

Electronic resources consulted:

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

fdabbs.fda.gov (login using name "bbs")

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

telnet gopher.who.ch  login:gopher)

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

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

Also available on the net, though I haven't had time to look at it online 
yet, is the Morbidity and Mortality Weekly Report (MMWR).  It is available
by Worldwide Web at:

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

htto:/wwww.crawford.com/cdc/mmwr/mmwr.htmi

and by gopher at Duke University.

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.

