Toward global Haemophilus influenzae type b immunization.

Received 2 September 2003; accepted 5 September 2003; electronically published 18 November 2003. Reprints or correspondence: Dr. Robert S. Daum, University of Chicago Children’s Hospital, MC 6054, 5841 S. Maryland Ave., Chicago, IL 60637-1470 ([email protected]). Clinical Infectious Diseases 2003; 37:1600–2 2003 by the Infectious Diseases Society of America. All rights reserved. 1058-4838/2003/3712-0004$15.00 Haemophilus influenzae type b (Hib) conjugate vaccines, consisting of the type b capsular saccharide covalently linked to a protein carrier or a bacterial protein membrane complex, were put into clinical use in the late 1980s. Prior to the introduction of these conjugate vaccines, Hib was the leading cause of meningitis, epiglottitis, and other life threatening bacterial infections in infants and young children in the US and other industrialized countries [1]. Since their introduction, the incidence of Hib disease in the US has decreased by 98% among children 5 years of age. A similar decrease has been achieved in the 21 other relatively affluent countries that had introduced the Hib vaccine into their immunization programs as of 2000 [2]. The significance of these accomplishments was appropriately recognized in 1996, when John Robbins, Rachel Schneerson, David Smith, and Porter Anderson, Jr., were jointly awarded the Lasker Award in Clinical Medical Research for developing Hib conjugate vaccines. Indeed, the near elimination of Hib disease in industrialized countries is arguably the major success story in pediatrics in the last 2 decades. Moreover, borrowing similar technology, conjugate vaccines for pneumococcal disease have been introduced with similarly impressive results. Meningococcal conjugate vaccines have had success in England and seem poised for expanded development and deployment. Due to the success of the Hib program in industrialized countries and the global burden of Hib disease, the World Health Organization (WHO) has encouraged the introduction of Hib vaccines worldwide [3]. Despite this, the majority of the world’s children still remain unvaccinated. The reasons for this poor rate of coverage in most developing countries are several: the lack of clear definitions, in many nations, of the epidemiology of Hib disease; a lack of agreement as to the disease burden threshold that should compel universal vaccination; and the expense of Hib conjugate vaccines. Prior to the introduction of any new vaccine, it is important to demonstrate a clear need for the intervention. Defining the incidence of Hib disease in developing countries has been difficult. There are several reasons for this difficulty. The bacteriology of Hib has remained challenging for many clinical microbiology laboratories, thus hindering the easy recognition of Hib as an etiologic agent. Optimal growth conditions require media supplemented with nicotinamide adenine dinucleotide and hemin, and they are not always available. Additionally, in many countries, antibiotics are frequently given to patients prior to diagnostic testing, and, in some locales, clinical practice for patients with presumed meningitis does not dictate routine lumbar punctures. Moreover, many children may not have access to medical facilities. Even if they reach a hospital or clinic, diagnostic capabilities are often not available [4, 5]. For these reasons, Hib disease may often be undetected. When this occurs, resistance to the need for an Hib vaccination program is understandable, because of a belief that there is a relatively low burden of Hib disease. This belief, whether correct or not, has influenced decision making in many areas of the world, particularly in Asia. It does seem clear, however, that Hib disease is present throughout many parts of Asia [2, 5, 6] and, most likely, throughout the world. The principal appears to be “the harder one looks, the more Hib disease one finds.” The additional issue of what prevalence threshold is sufficient for commitment to a vaccination program is an important one that will need to be addressed by individual public health authorities. Another important issue is that the epidemiology of Hib disease in many developing countries appears to differ from that in industrialized countries. In some developing countries, the incidence of in-