Centers for Disease Control and Prevention [CDC], the Food and Drug
Administration [FDA], and the Department of Health and Human Services
[HHS]) are working with the influenza vaccine companies in several
ways. Aventis Pasteur believes it has the capability to produce the
same or more doses of influenza vaccine for the 2005–2006 influenza season. In addition, MedImmune has indicated that it has the capability to produce 10 million doses of FluMist for the 2005–2006 influenza season and as many as 40 million doses by 2007. We will continue to work with Chiron Corporation, in close collaboration with the UK regulatory authorities, to help Chiron address, as quickly as possible, the manufacturing problems they experienced this year. In addition, FDA has been encouraging foreign licensed manufacturers to apply for US licensure and is providing clear pathways to efficiently reach this goal.
In each of its past 2 budget requests, HHS has asked for $100 million to shift vaccine development to new cell-culture technologies and to provide year-round availability of eggs for egg-based vaccine. We received $50 million in the FY04 budget for this activity and urge Congress to fully fund the $100 million request in the FY05 budget.
Under the Current Good Manufacturing Practices (cGMP) initiative, FDA is working with industry to encourage the use of advanced technologies as well as quality systems and risk-based approaches that build quality into the manufacturing process. FDA is also using the same quality systems and risk-based approaches to modernize our regulatory responsibilities with regard to manufacturing. For example, we are providing advanced training for manufacturing investigators.
FDA is taking an inventory of foreign manufacturing of US-licensed products that are critical to public health, such as influenza vaccine, and will put into place, as needed, information-sharing agreements with other national regulatory authorities. In addition, we recognize that public health needs and resources are increasingly global in nature; in the hope that vaccines can be licensed in multiple regions of the world, FDA has been encouraging more internationally harmonized product development.
We will also address in various populations the effectiveness of reduced doses of influenza vaccine, such as intradermal vaccination or using half the current dose intramuscularly. We will evaluate whether any of these approaches for increasing the available vaccine supply could be used in the near future.
A recently published
study reported an 18% frequency of neuraminidase-inhibitor resistance for
a small group of Japanese children treated with oseltamivir.
This is higher than the 5.5% resistance reported from a larger
outpatient pediatric oseltamivir treatment study in the United States (N=182).
It should be noted that the Japanese study detected resistance
inhibitors in young children (including outpatient and hospitalized
children), the dosage of oseltamivir used for young children in
Japan is lower than that used in the United States, the study was smaller
(N=50) than the US study, and the molecular methods used to determine
neuraminidase-inhibitor resistance were different than the standard
assays that are used worldwide. Nevertheless, this study in Japan
implications for use of oseltamivir, and continued surveillance
for neuraminidase-inhibitor resistance is warranted.
Only state health departments are eligible to request antiviral medications from
the Strategic National Stockpile (SNS). The SNS will review each
request; and after determining that sufficient attempts have been made
antiviral medications from distributors and manufacturers, it may
release influenza antiviral medications to the state. The state health
will determine how the medications should be distributed. In general,
they will only be for use in outbreak settings, such as an outbreak
in an institution, and the manner of treatment and chemoprophylaxis
will be at the discretion of the clinicians involved in the outbreak.
CDC guidelines for this are here.
information is available regarding the frequency and severity of influenza
illness or the benefits of influenza vaccination for persons with HIV
infection. Several reports indicate that influenza symptoms might be
prolonged and that the risk for complications from influenza increases
for certain HIV-infected persons. Influenza vaccination has been shown
to produce substantial antibody titers against influenza in vaccinated
HIV-infected persons who have minimal AIDS-related symptoms and high
CD4+ T-lymphocyte cell counts. A limited randomized, placebo-controlled
trial showed that influenza vaccine was highly effective in preventing
symptomatic, laboratory-confirmed influenza infection among HIV-infected
persons who had a mean of 400 CD4+ T-lymphocyte cells/mm3; a limited
number of persons who had CD4+ T-lymphocyte cell counts under 200 were
included in that study. A nonrandomized study among HIV-infected persons
determined that influenza vaccination was most effective for persons
with more than 100 CD4+ cells and for those with fewer than 30,000
viral copies of HIV type-1/mL. For persons who have advanced HIV disease
and low CD4+ T-lymphocyte cell counts, influenza vaccine might not
induce protective antibody titers; for these persons, a second dose
of vaccine does not improve the immune response. Because influenza
can result in serious illness and because influenza vaccination can
result in the production of protective antibody titers, vaccination
will benefit and is recommended for HIV-infected persons, including
HIV-infected pregnant women, regardless of their CD4+ cell count. For
more information, please see the Advisory Committee on Immunization
Practices recommendations for influenza vaccination.
Drug Assistance Program (ADAP) provides medications for the treatment
of HIV disease and provides
services that enhance access
and adherence to and monitoring of drug treatments. The program is
funded through Title II of the Ryan White Care Act, which provides
grants to states and territories. The ADAP in each state and territory
decides which medications will be included in its formulary and how
those medications will be distributed. At least one state has made
antiviral medications available in its formulary on an emergency
and temporary basis for this influenza season. For more information
There are at least 2 published studies on this topic; they address
safety and immune response but not vaccine effectiveness
directly. King et al
(J Infect Dis. 2000 Feb;181(2):725–8) studied 57 adults who were HIV infected (CDC class A1-2) and 54 adults who were not HIV-infected. Participants, who were not prescreened for influenza susceptibility, were randomly assigned to receive trivalent live attenuated influenza vaccine (LAIV) or placebo intranasally. LAIV was safe and well tolerated with no serious adverse events attributable to the vaccine. Rates of reactogenicity were similar for LAIV and placebo recipients except that runny nose/nasal congestion was significantly more common in LAIV recipients regardless of HIV status. No prolonged shedding of LAIV was observed in HIV-infected recipients. HIV RNA levels were not increased and CD4 counts were not decreased after immunization in HIV-infected LAIV recipients compared with placebo recipients. Shedding of LAIV and increases in antibody titers were infrequent, consistent with prior experience in unscreened adults. The data suggest that inadvertent vaccination with LAIV in relatively asymptomatic HIV-infected adults would not be associated with frequent significant adverse events.
This same group later reported on a similar, small study of
children (Pediatr Infect Dis J. 2001 Dec;20(12):1124–31).
They assessed the safety of LAIV administered to relatively asymptomatic or mildly
symptomatic HIV-infected children and to children not infected with HIV. They
found no significant differences in rates of reactogenicity events and vaccine-related
adverse events after receipt of the first dose of LAIV or placebo within each
HIV status group; they also found no differences after each dose of LAIV between
children who were HIV infected and not HIV infected. Overall, none of the HIV-infected
children experienced a significant LAIV-related serious adverse event or influenza-like
illness, making the one-sided 95% confidence interval (CI) of such a serious
event occurring after LAIV 0% to 12%. No significant changes in geometric mean
HIV RNA concentrations, CD4 counts, or CD4% or prolonged or increased quantity
of LAIV virus shedding occurred in HIV-infected children after receiving either
dose of LAIV. All recovered influenza isolates retained the temperature-sensitive
phenotype. After 2 doses of LAIV, 83% of the children who were not HIV infected
and 77% of the children who were HIV infected had a 4-fold or greater rise in
influenza antibody to at least 1 of the 3 LAIV strains.
On October 5,
2004, CDC and the Advisory Committee on Immunization Practices (ACIP) issued
interim influenza vaccine recommendations that targeted
8 priority groups for vaccination with this year’s limited supply
of vaccine. These groups included persons aged 2 to 64 years who
had chronic medical conditions (including persons with HIV/AIDS).
CDC has worked with Aventis Pasteur, the remaining supplier of inactivated
influenza vaccine, to allocate remaining vaccine to providers and
organizations that serve priority patients. Most recently, CDC is
working with state health departments on apportioning influenza vaccine
to them. The state health departments will in turn allocate vaccine
to providers and organizations best able to vaccinate priority patients.
CDC, FDA, and
HHS are also evaluating whether inactivated influenza vaccine licensed
in other countries could be purchased and used in the United States
under an Investigational New Drug (IND) protocol. As many as 5
million doses of vaccine may be available from these manufacturers; however,
even if this vaccine is approved for an IND, we would not expect
delivery of most of this vaccine until December 2004 and January
and ACIP have not recommended subprioritizing persons within
or across the priority groups mentioned in the interim influenza
For persons with HIV/AIDS, those with severe immunosuppression may
not mount an adequate antibody response. However, CD4 counts are
not clearly predictive of response or nonresponse to vaccination.
ideally all persons with HIV/AIDS should receive inactivated influenza
vaccine. Persons with advanced HIV disease may have a poor response
to immunization. Therefore, chemoprophylaxis (use of antiviral medications
for prevention) should be considered for these patients if they are
likely to be exposed to people with influenza. (CDC has developed
interim recommendations for the use of antiviral medications
during the 2004–2005 influenza season, available here).
disease, caused by Streptococcus pneumoniae, is a common cause
of bloodborne infection, meningitis, and pneumonia;
it commonly causes infection after influenza virus infections.
are 2 vaccines for preventing pneumococcal infections. One,
called Prevnar and manufactured by Wyeth Vaccines, is for children.
Prevnar is a
7-valent (containing antigens from 7 serotypes of S. pneumoniae
conjugate,vaccine. The other, called Pneumovax and manufactured
by Merck, is a 23-valent vaccine for older children (older
than 2 years)
and adults. Neither vaccine is a substitute for influenza vaccine,
but each can help prevent some common complications of influenza.
the pneumococcal conjugate vaccine, is recommended for all
children younger than 2 years and for children 2 to 4 years
of age who have
certain chronic illnesses or any immunocompromising condition.
Clinicians should consider giving the vaccine to all children
aged 2 to 4 years,
especially those who are 24 to 35 months of age, African American
or Native American, or attending group daycare.
conjugate vaccine prevents bacteremia, pneumonia, and otitis
media caused by pneumococci that are one of the vaccine serotypes.
It also reduces
carriage and transmission of vaccine-type pneumococci. Use
the vaccine in children has been shown to reduce cases of
invasive disease in adults.
recommends that all adults aged 65 and older and those aged
2 to 64 years who have an immunocompromising condition,
or certain underlying medical conditions be vaccinated against
pneumococcal disease with pneumococcal polysaccharide
vaccine. These persons include
most of the same persons in the CDC priority groups for influenza
vaccine during this season of influenza vaccine shortage.
is now in adequate supply. Given recent and prolonged shortages, many
children may not be adequately immunized. Parents and providers should make sure
that children are fully vaccinated. Although the full schedule recommended for
infants is 4 doses, a recent National Immunization Survey indicated that about
86% of children aged 19 to 35 months had received 1 or more doses, but only 67%
had received 3 or 4 doses.
A detailed list of the conditions that are indications and a
concise table of the vaccine schedule can be found
the sole manufacturer of pneumococcal polysaccharide vaccine,
that it currently has adequate supplies on hand and is tripling
normal production volumes to meet anticipated increase in demand.
Centers for Disease
Control and Prevention, 1600 Clifton Rd,
Atlanta, GA 30333, USA
800-CDC-INFO (800-232-4636) TTY: (888) 232-6348,
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