Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT00883012 |
| Other study ID # |
Paediatric influenza vax |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 4
|
| First received |
April 15, 2009 |
| Last updated |
April 2, 2012 |
| Start date |
February 2009 |
| Est. completion date |
June 2010 |
Study information
| Verified date |
April 2012 |
| Source |
University of Witwatersrand, South Africa |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
South Africa: Human Research Ethics CommitteeSouth Africa: National Health Research Ethics Council |
| Study type |
Interventional
|
Clinical Trial Summary
Influenza associated pneumonia causes significant morbidity in young HIV-infected children.
Although annual vaccination against influenza is recommended for HIV infected children, it
has not been implemented as routine care, due to the lack of data on disease burden and
vaccine efficacy.
This study aims at determining the effectiveness of influenza vaccination in HIV infected
children in South Africa.
Description:
Influenza virus infects 30 to 50% of children under five years of age during the course of
any epidemic. The attack rates of influenza virus associated illness during infancy remains
high, and at least 50% of influenza associated hospitalisation amongst children occurs in
infants <6 months of age. Approximately 33% of children would have been infected at least
once during their first year of life. The estimated attack rates in children aged 0-5 and
6-12 months for influenza illness is 12.4/100 and 20.3/100 child years respectively.
Influenza virus causes LRTI amongst 89% of children infected in the 6-12 month age group.
The risk of influenza infection is higher amongst older children (2-5 years of age);
however, the risk of developing LRTI (78 versus 2.5 per 100 child years) is greater amongst
younger children (< 2 years of age).
In South Africa, the burden of influenza associated pneumonia has been characterized in HIV
infected children. The incidence of severe pneumonia in which influenza virus was identified
was 8.03 fold (95%CI 5.05-12.76) greater in HIV infected compared to HIV non-infected
children (1 268 versus 148 per 100 000 child years) aged < 2 years. These rates however
provide a very conservative estimate as to the burden of influenza illness, since it
excludes children with influenza illness that were hospitalized for syndromes other than
pneumonia as well as children managed as outpatients. Furthermore, although the duration of
hospitalization for influenza associated pneumonia was similar between HIV infected and HIV
uninfected children (median 4-5 days), there was a statistically non-significant increased
risk of mortality among HIV infected children (8.0% versus 2.2%; P=0.20). Much of the
differences in morbidity and mortality in HIV infected individuals with influenza-associated
pneumonia may be due to contribution of other co-existing pathogens.
Recommendations made by the Advisory Committee on Immunization Practices (ACIP) advocating
the annual use of the subunit influenza vaccine in HIV-1 infected children are largely
founded on the theoretical concern regarding the potential severity of influenza disease in
HIV-1 infected children. Although vaccination with the subunit influenza vaccine is
recommended for HIV-1 infected children >6 months of age, there are concerns regarding the
benefits of vaccination in these children. These include that in addition to a poor immune
response to the vaccine, particularly in severely immunocompromised HIV-1 infected children,
increases in plasma HIV RNA following vaccination have been described. The increase in
plasma HIV RNA was transient and does not appear to be of any long-term clinical
significance. Recently a few studies, with partly conflicting results, have been undertaken
evaluating the immunogenicity of influenza vaccination in children on antiretroviral
therapy. However, no such studies have been undertaken in Africa or Asia where the burden of
paediatric HIV is the greatest.
The routine use of influenza vaccine in HIV infected children remains low, partly related to
the lack of adequate data regarding the burden of influenza associated disease in these
children as well as the lack on any vaccine-efficacy data in HIV infected children.
Determining the burden of disease and effectiveness of influenza vaccine in HIV infected
children will have a bearing on routine immunization recommendations as well as planning for
future influenza pandemics.
Differences in the epidemiology of HIV between developing and developed countries in which
the prevalence of HIV is low to that of high-burden sub-Saharan African countries makes it
necessary to be cautious in extrapolating data and recommendations of developed countries to
developing countries. These differences may include: i. differences in standard of care,
including access to prophylaxis against opportunistic infections and use of highly active
anti-retroviral therapy (HAART); ii. differences in risk for disease from opportunistic
pathogens, e.g. Mycobacterium tuberculosis, etc. These differences may all contribute to
differences in the risk and severity of influenza illness among HIV infected individuals
from these communities as well as possibly responsiveness and effectiveness of vaccination.
It is within this context that this study aims at determining the effectiveness of influenza
vaccination in HIV infected children in South Africa. The significance of the findings from
this study will help quantify the burden of influenza illness in African HIV infected
children, in the era of HAART, as well as assist in making more informed recommendations for
the use of influenza vaccine in HIV infected children and in guiding national policy for
preparing for a future influenza virus-pandemic.
350 Patients will be recruited at Chris Hani-Baragwanath Hospital, Soweto, South Africa onto
this prospective, double-blind, placebo randomised controlled trial evaluating the efficacy
of a tri-valent sub-unit influenza vaccine in HIV infected children. Participants will be
randomized to receive either two doses of Influenza sub-unit vaccine or placebo one month
apart, preceding the 2009 Influenza season. 100 children will be included into the
immunogenicity cohort, and have blood drawn to evaluate baseline influenza strain specific
antibody levels and subsequent levels one-month following the first and second doses of
study vaccine.
Study participants will be followed up during the course of the influenza season, which will
be defined as starting 1st May 2009 and ending 30th September 2009. Subjects will be
contacted weekly to determine whether they fulfill the criteria for Influenza-like illness.
Subjects who fulfill the criteria for diagnosing ILI will be requested to come into the
clinic within 48 hours for further investigation, which will involve a nasopharyngeal
aspirate (for identification of respiratory viruses), nasopharyngeal swab (for
identification of Streptococcus pneumoniae colonization) and blood draw (for culture and
Streptococcus pneumoniae testing).
