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April
2007: VOLUME
1, NUMBER 6
Community
Mitigation of Pandemic Influenza
In this issue...
Recent
events related to the unprecedented outbreak of H5N1 avian influenza
in Eurasia and Africa as well as new information about the 1918 pandemic
have prompted a great deal of apprehension that the next influenza pandemic
may be imminent. Because a strain-specific vaccine is expected to be
unavailable and antivirals are expected to be in limited supply in the
first wave of a new pandemic, much attention has been focused on public
health interventions that may arrest, slow or at least diminish the
magnitude of any such outbreak. In this issue, we review the current
literature related to what is known about influenza transmission and
which public health disease containment measures are likely to work. |
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Course
Directors
John
G. Barlett, MD
Professor of Medicine
Department of Medicine
The Johns Hopkins
University
School of Medicine
Jason
E. Farley, PhD(c), MPH, NP
Adult Nurse Practitioner,
Infectious Disease
Clinical Instructor
Department of Medicine
The Johns Hopkis
University
School of Nursing |
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GUEST
EDITOR OF THE MONTH |
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Commentary
& Reviews:
Eric
S. Toner, M.D.
Senior
Associate
Center
for Biosecurity of the University of Pittsburgh Medical Center
Pittsburgh,
PA |
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Guest
Faculty Disclosure
Eric
S. Toner, M.D., has disclosed that he has no relationship
with commercial supporters.
Unlabeled /Unapproved Uses
The author has indicated that there will be no reference
to unlabeled/ unapproved uses of drugs or products in this presentation. |
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The
Johns Hopkins University School of Medicine and The Institute for
Johns Hopkins Nursing take responsibility for the content, quality,
and the scientific integrity of this CE activity.
At the conclusion of this activity, participants should be
able to: |
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Describe
both the known and unknown factors about the transmission of influenza; |
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Identify
the primary community mitigation strategies under current consideration; |
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Discuss
the strengths and weaknesses inherent in using modeling to create
public health policy. |
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COMPLETE
THE POST TEST
Step 1.
Click on the appropriate link
below. This will take you to the post-test.
Step 2.
If you have participated in a
Johns Hopkins on-line course, login. Otherwise, please register.
Step 3.
Complete the post-test and course
evaluation.
Step 4.
Print out your certificate.
Pharmacy credit is only available via PDF mail-in form:
 |
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The
Department of Health and Human Services’ planning assumptions for an
unmitigated and severe (1918-like) pandemic include 9.9 million hospitalizations
in the US with 1.5 million patients requiring intensive care, figures
which are several times the available capacity of the healthcare system[1].
In fact, the US healthcare system would be seriously challenged by
even a mild pandemic[2]. For this reason, public health
interventions which might reduce this disease burden have attracted
much interest.
The use of such interventions,
collectively, has been referred to by a variety of names, including
community mitigation, disease mitigation, and community containment.
Some authors include in these terms the use of limited amounts of vaccine
and antivirals; others include only non-pharmaceutical interventions
(NPIs). Among the NPIs being considered are use of masks, hand washing,
isolation of the sick and quarantine of the exposed, travel restrictions,
and various means of social distancing. Included in the category of
social distancing are cancellation of large gatherings, closing public
places, and closing schools[3].
The fundamental question is whether
such interventions will work, at what cost and who will pay. Since the
world has not experienced a severe pandemic in 90 years, there is little
direct experience to draw upon. And, surprisingly, as is clearly demonstrated
in the paper by Brankston et al, very little experimental research has
been done on influenza transmission, and none of the proposed interventions
have been tested in a controlled fashion. As such, the purported benefits
of most of the community mitigation strategies under discussion are
derived from computer modeling, the results of which depend on unproven
assumptions about flu transmission and the efficacy of the various interventions[4,5].
The CDC has recently issued its
Interim Pre-Pandemic Planning Guidance: Community Strategy for Pandemic
Influenza Mitigation in the United States – Early, Targeted, Layered
Use of Nonpharmaceutical Interventions[6]. The strategy calls
for a flexible response depending on the severity of the pandemic. While
the interventions suggested include isolation of the sick, voluntary
quarantine of contacts, and adult social distancing, the heaviest reliance
is on early and prolonged school closure in the setting of a severe
pandemic.
Given the potentially dire consequences
of a pandemic, it is reasonable to attempt to reduce the impact of the
outbreak by whatever means are available if those means have a reasonable
chance of being effective, and if the collateral consequences of their
use is well understood and acceptable. At this time, as is shown in
the papers by Germann, Haber and Ferguson, there is little empirical
evidence to support most of the NPIs being recommended. Further, the
modeling studies give inconsistent results (depending upon the assumptions
used), and the societal and economic consequences of their use have
not been studied.
While the urge to “do something” in the face of an impending pandemic
is understandable, caution is advised and we would do well to remember
the first dictum of medicine — primum non nocere (first, do
no harm). One such action that would clearly have only beneficial consequences
would be to better prepare our woefully unprepared hospitals[7].
References
| 1. |
HHS Pandemic
Influenza Plan. November 3, 2005. |
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| 2. |
Toner
E, Waldhorn R, Maldin B, et al. Hospital
preparedness for pandemic influenza. Biosecurity and Bioterrorism
2006; 4(2). |
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| 3. |
Inglesby
T, Nuzzo J, O’Toole T, Henderson D. Disease
mitigation in the control of pandemic influenza. Biosecurity
and Bioterrorism 2006;4 (4): 366-375. |
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| 4. |
Institute
of Medicine. Modeling
community containment for pandemic influenza. 2006. National
Academies Press. |
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| 5. |
WHO
writing group. Nonpharmaceutical
interventions for pandemic influenza, national and community measures.
Emerg Inf Dis 2006;12:88-94. |
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| 6. |
CDC. Interim
Pre-pandemic Planning Guidance: Community Strategy for Pandemic
Influenza Mitigation in the United States—Early, Targeted, Layered
Use of Non-Pharmaceutical Interventions. |
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| 7. |
Toner
E, Waldhorn R. What
hospitals should do to prepare for an influenza pandemic. Biosecurity
and Bioterrorism 2006;4 (4). |
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MODELING
MITIGATION MEASURES IN A SMALL TOWN |
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Haber
M, Shay D, Davis X et al. Effectiveness of interventions
to reduce contact rates during a simulated influenza pandemic.
Emerg Inf Dis 2007;13 (4).
(For non-journal subscribers, an additional fee may apply
for full text articles.) |
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The
investigators in this study used a computer model to simulate an
influenza outbreak in a small US town assuming no vaccine or antivirals
were available. The model tested the effect of school closings, confinement
of the sick and their household contacts, and reductions in contact
rates of long term care facilities. The model used a basic reproductive
number (R0) of 2.7. This is the number of people infected by a source
patient at the onset of an outbreak to which everyone is susceptible.
In other words, each infected individual on average infects 2.7 other
people. In various simulations, school closed when 10, 15 or 20%
of the children were sick, and remained closed for 7, 14 or 21 days.
The model assumed an attack rate of 62% among school age children.
The model also assumed that kids not in school had increased contacts
with others outside of school. Both the delay in confinement of the
sick after the onset of symptoms and the confinement compliance rate
could be varied as well.
When school were
closed relatively early on (when 10% were sick) and remained closed
for 14 days the rate of illness in the community dropped from 32%
to 26%. However, when a school closing threshold of 20% was used
instead, the rate of illness did not significantly change. If 60%
of the sick confined themselves to home 2 days after the onset of
symptoms, there was a 33% decrease in illness in the community. This
decrease figure rose to 80% if household contacts were also quarantined.
The authors conclude
that voluntary isolation (withdrawal to home) of ill persons is a
more effective strategy than closing schools in reducing the impact
of a pandemic. The disease burden in the community can be further
reduced by voluntary home quarantine of household contacts. The relative
lack of efficacy of school closing found in this model (compared
to some other models) is related to the fact that Hays’ model assumes
schools will not close until at least 10% of kids are sick, and that
students who are out of school will have increased household and
community interactions. Other models assume that schools will close
earlier in the outbreak and that kids out of school will remain segregated. |
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WHAT
IS KNOWN ABOUT INFLUENZA TRANSMISSION |
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Brankston
G, Hirji Z, Lemieux C, Gardam M. Transmission of Influenza
A in human beings. Lancet Inf Dis 2007; 7(4):257-65.
(For non-journal subscribers, an additional fee may apply for
full text articles.) |
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Despite
70 years of research on influenza, debate continues about even the most
basic facts pertaining to influenza transmission. These include whether
the virus is spread primarily by a respiratory or contact route and,
if respiratory, whether it is by large droplets that travel a few feet
or by small aerosols that can remain suspended for long distances and
a prolonged time. Because key decisions about infection control and
disease containment depend upon an accurate understanding of the mode
of transmission of influenza, Brankston et al set out to assess the
actual scientific basis of commonly held assumptions. They undertook
a systematic review of the English language experimental and epidemiological
literature pertaining to the mode of transmission of influenza in mammals.
Of 2012 initial citations found, only 32 articles were ultimately felt
to be relevant after review by at least two researchers. These 32 articles
were then analyzed in detail and abstracted.
Six experimental studies examined
the survival of aerosolized influenza in the environment, demonstrating
that various influenza strains remain viable after artificial aerosolization
and can infect several cell types. Additionally, studies found that
while some influenza virus can be detected in the air for up to 1 to
24 hours after aerosolization (depending upon the relative humidity),
the concentration in the air drops fairly quickly. Two studies demonstrated
that the virus can survive on non-porous surfaces for several hours.
No studies, however, looked at whether humans can be infected by contact
with contaminated surfaces.
Thirteen studies showed that
clinical influenza can be produced in humans and a variety of other
mammals by exposure to an artificial aerosol containing influenza virus.
Four studies demonstrated that these aerosol-infected animals can then
transmit the infection secondarily to other animals. One study showed
that virus can be found in the air around infectious animals. No study
has looked at person-to-person transmission after artificial infection.
One study showed that influenza can be transmitted between mice separated
by 2 cm by double wire mesh, and that the rate of infection was no different
than if they were housed in the same cage. Another study showed that
influenza can be transmitted between ferrets connected only by a 2.5
m long S-shaped tube.
Nine observational studies were
found that examined natural outbreaks of influenza in people. Three
of the studies suggested the possibility of airborne (aerosol) transmission
and six of the studies were more suggestive of a primarily droplet or
contact route of transmission. Four studies suggested the need for close
person-to-person contact. All the studies were confounded by multiple
factors and none could be considered definitive. Only one study was
found that reported on the use of control measures in a hospital outbreak
that was not confounded by use of vaccine or antivirals. That outbreak
ceased after implementation of isolation of infected patients, cohorting
of staff, and droplet and contact(but not airborne [aerosol]) precautions.
In summary, no studies were found
that demonstrated clear evidence of contact transmission; although none
disproved it either. Several studies showed a relationship between close
proximity and transmission which could result from contact, large respiratory
droplets or small particle aerosols. Artificial aerosol transmission
has been demonstrated in people and in animals, but whether natural
aerosols behave in the same manner is not known. Natural aerosol transmission
has been documented in ferrets, but since species differ in their relative
susceptibility to infection one must be cautious in extrapolating from
one species to another.
In the end, all that can be concluded,
other than that much more research is needed, is that transmission of
flu in humans is probably primarily by a respiratory route, that infection
usually results from close proximity, and that droplet precautions seem
to be sufficient to prevent infection. It should be noted that studies
involving seasonal influenza, to which there is widespread immunity
in the population, may not be applicable to a completely novel pandemic
virus to which no one has immunity. |
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MODELING
MEASURES TO MITIGATE NATIONAL SPREAD OF INFLUENZA |
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Germann
T, Kadau K, Longini I, Maken C. Mitigation strategies for
pandemic influenza in the United States. PNAS 2006;103(15):5935-5940.
(For non-journal subscribers, an additional fee may apply for
full text articles.) |
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Ferguson
N, Cummings D, Fraser C, et al. Strategies for mitigating
an influenza pandemic. Nature 2006;442:448-452.
(For non-journal subscribers, an additional fee may apply for
full text articles.) |
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Germann
and colleagues performed a computer modeling study that examined the
spread of an influenza pandemic across the entire US, and investigated
the impact of several mitigation interventions, including travel restrictions,
school closings, and targeted use of limited amounts antivirals and
vaccine. The R0 was varied from 1.6 to 2.4.
Similarly, Ferguson and his colleagues
created a computer simulation that modeled the spread of influenza across
the US and the UK assuming an R0 of 1.7-2.0. They examined the impact
of travel restrictions, school closure, case isolation and quarantine,
and targeted use of vaccine and antivirals.
The Germann study found that
travel restrictions had minimal impact: imposition of a 90% reduction
in domestic travel only slowed the spread of the virus by a few days
and had no affect on the eventual size of the outbreak. The Ferguson
group found similar results.
School closure, in the Germann
study, was found to have significant impact only if R0 was set at 1.6
and schools closed within 7 days of the onset of the pandemic. For larger
values of R0, school closure and other attempts at social distancing
only slowed the spread of the virus modestly and did not affect the
total number of sick. Likewise, Ferguson found that although school
closure could reduce peak attack rates by 40%, it had little impact
on overall attack rates.
Germann’s group found that for scenarios involving an R0 value of 1.6,
targeted use of antivirals to treat the sick and prophylaxis of household
contacts proved an effective strategy. If, however, R0 was set at 1.8
or above, the amount of antivirals needed became probative. Ferguson
also found that early treatment with antivirals could have a modest
but significant impact, but only if 90% of cases are treated within
1 day of the onset of symptoms. If antiviral treatment was delayed by
more than 1 day, there was little reduction in attack rates. Ferguson
also found antiviral prophyaxis of household contacts to be a highly
effective strategy, but noted that implementation would require stockpiling
enough antivirals for half the population.
Both studies found that early,
targeted use of limited amounts of vaccine, even if was not very effective,
significantly reduced the number of sick. This was especially true if
the vaccine was used preferentially in schools. Germann found, however,
that this was only the case if the R0 was less than1.9. In both studies
it was assumed that vaccination could start very early in the outbreak
(within 2 weeks) and proceed at a rapid rate (10-21 million vaccinations
per week).
These studies demonstrate two
important points. First, they show how difficult it is to reduce the
impact of a pandemic using community mitigation measures. Both models
show that only very aggressive, and perhaps unrealistic, interventions
are likely to be effective in reducing the disease burden in a pandemic – and
then only if the virus is not very transmissible. Early isolation and
treatment of the sick, and confinement and prophylaxis of contacts,
were found to be the most effective strategies. School closure was found
to have relatively little impact, and then only if the children were
separated while out of school. Targeted vaccination of school children
(assuming schools are not closed) also appeared to be effective in some
cases, but only if vaccination could be started immediately and proceed
very quickly
Secondly these studies show how
sensitive models can be to small alterations in the assumptions used.
Almost any intervention appears to work if R0 is less than 1.6 and few,
if any, work if R0 is set at >2.0. Since estimates of R0 for the previous
pandemics vary from 1.6 to 3, and the R0 of a novel pandemic virus that
has not yet emerged can only be guessed at, the suggested beneficial
effects of the interventions modeled in these studies must be taken
with a grain of salt. |
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| Accreditation
Statement · back
to top |
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This
activity has been planned and implemented in accordance with the
Essential Areas and Policies of the Accreditation Council for Continuing
Medical Education through the joint sponsorship of the Johns Hopkins
University School of Medicine and The Institute for Johns Hopkins
Nursing. The Johns Hopkins University School of Medicine is accredited
by the ACCME to provide continuing medial education for physicians.
The Institute for
Johns Hopkins Nursing is accredited as a provider of continuing nursing
education by the American Nursing Credentialing Center's Commission
on Accreditation. |
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| Credit
Designations · back
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Physicians
The Johns Hopkins
University School of Medicine designates this educational activity
for a maximum of 1.0 AMA PRA Category 1 Credit(s)TM.
Physicians should only claim credit commensurate with the extent
of their participation in the activity.
Nurses
This 1.0 contact
hour Educational Activity (Provider Directed/Learner Paced) is provided
by The Institute for Johns Hopkins Nursing. Each Newsletter carries
a maximum of 1.0 contact hours or a total of 12.0 contact hours for
the twelve newsletters in this program.
Pharmacists
 This
program is approved for two hour credit (0.2 CEUs) and is co-sponsored
by the University of Tennessee College of Pharmacy is accredited
by the Accreditation Council for Pharmacy Education as a provider
of continuing pharmacy education. A statement of CE credit will be
mailed within 4 weeks of successful completion and evaluation of
the program. ACPE Program #064-999-06-275-H01.
Grievance Policy: A participant, sponsor, faculty
member or other individual wanting to file a grievance with respect
to any aspect of a program sponsored or co-sponsored by the UTCOP
may contact the Associate Dean for Continuing Education in writing.
The grievance will be reviewed and a response will be returned within
45 days of receiving the written statement. If not satisfied, an
appeal to the Dean of the College of Pharmacy can be made for a second
level of review. |
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| Post-Test
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| To
take the post-test for eInfluenza Review you will need to visit The
Johns Hopkins University School of Medicine's CME website or The
Institute for Johns Hopkins Nursing. If you have already registered
for another Hopkins CME program at these sites, simply enter the
requested information when prompted. Otherwise, complete the registration
form to begin the testing process. A passing grade of 70% or higher
on the post test/evaluation is required to receive CME/CNE credit. |
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| Statement
of Responsibility · back
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| The
Johns Hopkins University School of Medicine and The Institute for
Johns Hopkins Nursing take responsibility for the content, quality,
and scientific integrity of this CME/CNE activity. |
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| Target
Audience · back
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| This
activity has been developed for the Primary Care Physician, Internist,
Infectious Disease Specialists and Nurse. There are no fees or prerequisites
for this activity. |
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| Learning
Objectives · back
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The
Johns Hopkins University School of Medicine and The Institute
for Johns Hopkins Nursing take responsibility for the content,
quality, and the scientific integrity of this CE activity.
At the
conclusion of this activity, participants should be able to: |
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Describe
both the known and unknown factors about the transmission of
influenza; |
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Identify
the primary community mitigation strategies under current consideration; |
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Discuss
the strengths and weaknesses inherent in using modeling to create
public health policy. |
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| Internet
CME/CNE Policy · back
to top |
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The
Offices of Continuing Education (CE) at The Johns Hopkins University
School of Medicine and The Institute for Johns Hopkins Nursing are
committed to protect the privacy of its members and customers. The
Johns Hopkins University maintains its Internet site as an information
resource and service for physicians, other health professionals
and the public.
The Johns Hopkins
University School of Medicine and The Institute for Johns Hopkins
Nursing will keep your personal and credit information confidential
when you participate in a CE Internet based program. Your information
will never be given to anyone outside The Johns Hopkins University
program. CE collects only the information necessary to provide you
with the service you request. |
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| Faculty
Disclosure · back
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It
is the policy of The Johns Hopkins University School of Medicine
and The Institute for Johns Hopkins Nursing that the faculty and
provider disclose real or apparent conflicts of interest relating
to the topics of this educational activity, and also disclose discussions
of unlabeled/unapproved uses of drugs or devices during their presentation(s).
Johns Hopkins School of Medicine OCME and The Institute for Johns
Hopkins Nursing has established policies in place that will identify
and resolve all conflicts of interest prior to this educational
activity. Detailed disclosures will be made in the course handout
materials.
The presenting faculty
reported the following:
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John
G. Bartlett, MD, has disclosed that he has served on the HIV
Advisory Board for Glaxo Smith Kline, Abbott and Bristol-Myers
Squibb. |
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Jason
E. Farley, PhD(c), MPH, NP has disclosed that he has no relationship
with commercial supporters. |
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| Disclaimer
Statement · back
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| The
opinions and recommendations expressed by faculty and other experts
whose input is included in this program are their own. This enduring
material is produced for educational purposes only. Use of Johns
Hopkins University School of Medicine name implies review of educational
format design and approach. Please review the complete prescribing
information of specific drugs or combination of drugs, including
indications, contraindications, warnings and adverse effects before
administering pharmacologic therapy to patients. |
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© JHUSOM,
IJHN, and eInfluenza Review
Created by DKBmed. |
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COMPLETE
THE POST TEST
Step 1.
Click on the appropriate link below. This
will take you to the post-test.
Step 2.
If you have participated in a Johns Hopkins
on-line course, login. Otherwise, please register.
Step 3.
Complete the post-test and course evaluation.
Step 4.
Print out your certificate.
Pharmacy credit is only available via PDF mail-in form:
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