Walter R. Dowdle

Prevalence of Antibody to Current Influenza Viruses and Effect of Vaccination on Antibody Response

The extent of antibody to the influenza virus A/Hong Kong/68 (H3N2) after four years of prevalence was investigated in Britain and in the U.S.A. The results indicated a high incidence in both populations. The prevalence of antibody to a variant A/England/42/72 (H3N2) which has been causing epidemics of influenza in the southern hemisphere during the middle months of 1972 was also investigated. The differences reflect the shift in antigenic content of this variant, and although the overall proportion of the sera with antibody at > 1/40 was 37%, some age groups had an incidence of only 20% or less with antibody at this level. A commercial inactivated A/Hong Kong/68 influenza vaccine was given to a group of volunteers in Britain to see how effective it might be in stimulating antibody to the variant A/England/42/72. The antibody responses were better than expected from earlier vaccine studies, and 63% of the vaccinees developed antibody to the A/England/42/72 to levels thought likely to be protective. This suggested that until a vaccine made with the variant A/England/42/72 becomes available the present A/Hong Kong/68 vaccine would be of use to protect those at special risk this winter.

Antigenic Variants of Influenza B Virus

From 1967 to 1971 little antigenic variation was detected in the prevalent influenza B viruses but in December 1972 a new antigenic variant of influenza B was isolated in Hong Kong from sporadic cases of influenza. The new variant, B/Hong Kong/5/72, possessed a haemagglutinin antigen which showed considerable antigenic differences from that of former influenza B strains while its neuraminidase antigen was closely related to that of the earlier, 1967-71, isolates. The B/Hong Kong/5/72 variant became the predominant influenza B strain in the United Kingdom by early summer 1973, and in both the United Kingdom and Japan this strain was associated with outbreaks of influenza. Strains antigenically intermediate between the 1967-71 isolates and B/Hong Kong/5/72 were isolated in a number of countries, often concurrently with B/Hong Kong/5/72-like strains. Serological studies indicated that antibody to B/Hong Kong/5/72 was infrequent in the populations in the United Kingdom and the U.S.A., suggesting the possibility of future epidemic activity associated with the new variant. In addition, conventional inactivated influenza vaccines containing the older influenza B isolates given to volunteers stimulated poor antibody responses to B/Hong Kong/5/72 virus. These studies indicate the desirability of immunizing high risk patients against B/Hong Kong/5/72-like viruses before the coming influenza season. Vaccine containing the new variant influenza B strain are currently available in the United Kingdom.

A public-private partnership for malaria control: lessons from the Malarone Donation Programme

In 1996, Glaxo Wellcome offered to donate up to a million treatment courses annually of Malarone, a new antimalarial, with a view to reducing the global burden of malaria. The Malarone Donation Programme (MDP) was established the following year. Eight pilot sites were selected in Kenya and Uganda to develop and evaluate an effective, locally sustainable donation strategy that ensured controlled and appropriate use of Malarone. The pilot programme targeted individuals who had acute uncomplicated Plasmodium falciparum malaria that had not responded to first-line treatments with chloroquine or sulfadoxine-pyrimethamine. Of the 161 079 patients clinically diagnosed at the pilot sites as having malaria, 1101 (0.68%) met all the conditions for participation and received directly observed treatment with Malarone. MDP had a positive effect at the pilot sites by improving the diagnosis and management of malaria. However, the provision of Malarone as a second-line drug at the district hospital level was not an efficient and effective use of resources. The number of deaths among children and adults ineligible for MDP at the pilot sites suggested that high priority should be given to meeting the challenges of malaria treatment at the community level.

Will containment of wild poliovirus in laboratories and inactivated poliovirus vaccine production sites be effective for global certification

The absolute laboratory containment of any virus cannot be guaranteed, but a wealth of experience indicates that effective containment of wild poliovirus materials for global certification is technically and operationally feasible. Effective containment is based on the principles of minimal wild poliovirus infectious and potentially infectious materials in laboratories; minimal risks of operations in laboratories and inactivated poliovirus vaccine production facilities; minimal susceptibility of workers to wild poliovirus infection and shedding; and minimal susceptibility of populations to wild poliovirus spread. Each principle alone is imperfect, but collectively they greatly minimize the risks of transmitting wild poliovirus from the laboratory to the community.

Can post-eradication laboratory containment of wild polioviruses be achieved?

The purpose of containment is to prevent reintroduction of wild polioviruses from laboratories into polio-free communities. In order to achieve global commitment to laboratory containment the rationale should be clear and compelling; the biosafety levels should be justified by the risks; and the objectives should be realistic. Absolute containment can never be assured. Questions of intentional or unintentional non-compliance can never be wholly eliminated. Effective laboratory containment is, however, a realistic goal. Prevention of virus transmission through contaminated laboratory materials is addressed by WHO standards for biosafety. The principal challenge is to prevent transmission through unrecognized infectious laboratory workers. Such transmission is possible only if the following conditions occur: infectious and potentially infectious materials carrying wild poliovirus are present in the laboratory concerned; a laboratory operation exposes a worker to poliovirus; a worker is susceptible to an infection that results in the shedding of poliovirus; and the community is susceptible to poliovirus infections. At present it is difficult to envisage the elimination of any of these conditions. However, the risks of the first three can be greatly reduced so as to create a formidable barrier against poliovirus transmission to the community. Final biosafety recommendations must await post-eradication immunization policies adopted by the international community.

Haemagglutinin relationships of Hong Kong (H3) and Asian (H2) influenza strains delineated by antigen-specific recombinants.

Summary Reports by others have described the haemagglutinins of Hong Kong (H3N2) strains and the Asian (H2N2) strains as being antigenically unrelated. Cross reactions seen by the haemagglutination-inhibition (HI) test have been attributed to antibodies to a second major surface antigen, the neuraminidase, which is common to both subtypes. However, observations on human anamnestic antibody responses suggest the two haemagglutinins are related. In the present study we reexamined the antigenic relationship of these viruses using haemagglutinin specific virus recombinants, chicken and ferret antisera, antibody equilibrium filtration methods, and cross-infection in ferrets. Data from these studies consistently demonstrated an asymmetric relationship, independent of the neuraminidase, between the H2 and H3 strains.

National Inventory of Biomedical Laboratories That May Possess Wild Poliovirus Materials

The Department of Health and Human Services, in partnership with other Departments and Agencies of the Executive Branch, has announced a national wild poliovirus inventory of all biomedical laboratories that may possess wild poliovirus infectious or potential infectious materials. The inventory is scheduled to begin October 2002. Responses are due December 31, 2002. The national inventory alerts laboratories to the anticipated successful eradication of polio and encourages destruction of all unneeded wild poliovirus materials. Laboratories that retain poliovirus materials will be placed on the national inventory and kept informed of eradication progress and when to implement containment procedures. This paper summarizes information from the WHO Global Action Plan for Laboratory Containment of Wild Polioviruses (WHO, 2002) and the U.S. Strategy for Implementing Phase I of the Global Action Plan: The National Inventory (DHHS, 2002). Additional information can be accessed at the Poliovirus Laboratory Containment Preparedness web site, www.cdc.gov/od/nvpo/polio.