Prevention of Haemophilus influenzae Type b Infections in Apache and NavajoChildren

Abstract

Prospective surveillance of Haemophilus influenzae type b (Hib) disease has been done since 1981 in two high-risk populations, White Mountain Apaches and Navajos. The attack rate in children less than 5 years of age is 5-10 times higher than in the general US population. Three vaccines were evaluated. Unconjugated Hib capsular polysaccharide produced lower antibody responses in 18- and 24-month-old Apache infants than in white infants. HbOC (Hib oligosaccharide covalently linked to the nontoxic mutant diphtheria toxin CRM197) produced low antibody responses in Navajo infants after one or two doses but induced responses similar to those in whites after three doses. The responses of 18-month-old Navajos to HbOC were lower than those of whites, but most achieved protective levels. PRP-OMP (Hib capsular polysaccharide linked to the outer membrane protein complex of Neisseria meningitidis) produced good immune responses in 2-month-old Navajo and Apache infants after a single dose. This vaccine was greater than 90% efficacious in protecting Navajo infants from Hib disease when given at 2 and 4 months of age. Even a single dose achieved a high protective efficacy.

Vaccines based on the cell surface carbohydrates of pathogenic bacteria

“…On the other hand, PRP-OMP (which used a complex of meningococcal outer membrane proteins as the carrier) proved particularly effective in this population, perhaps because a protective antibody response is elicited after the first dose (Figure 3). Whilst different target populations can react in quantitatively different ways (Santosham et al 1992), the clear conclusion was that the Hib conjugate vaccines produced by a variety of routes are efficacious in the prevention of disease. Because of the low incidence of meningococccal disease in the UK and the well-established correlation between antibody level and protection (Goldschneider et al 1969a, b), licensing of meningococccal group C conjugate vaccines in the UK was on basis of immunogenicity, and particularly functional antibody levels as measured by a bacteriocidal assay, rather than protection against disease.…”

A defective Vkappa A2 allele in Navajos which may play a role in increased susceptibility to haemophilus influenzae type b disease.

“…Before the recent advent of conjugate vaccines, it was documented that 2.5% of Southwest Alaskan Eskimo children under 12 mo of age develop Hib disease, and overall the disease was fivefold more prevalent than in control North American populations (16). The ability to respond to Hib immunization with a robust antibody response has also been shown to have a genetic component, and may play an important role in the genetic susceptibility to disease (22)(23)(24). The ability of Navajos to respond to Hib polysaccharide vaccination is Ͼ 10 fold lower than age matched white children, correlating with their high rate of Hib disease.…”

The epidemiology ofHaemophilus influenzaetype b disease in the Republic of Ireland

“…The annual incidence of Hib disease in Ireland was similar to that experienced in England and Wales [8], Scotland [13] and France [12], lower than that in northern Europe [2, 1 1], Australia and New Zealand [6] and American populations of European origin [9], and substantially lower than rates experienced in native American [14,15] aboriginal [16] and African [34] children. The pattern of illness in the ROI differs somewhat from that of Hib disease in the UK with meningitis comprising a smaller proportion (45 %) in Irish children compared to 71 % in Oxford [4], 62 % in Gwynedd [5] and 56 % in England and WAales [8].…”

“…The age distribution of disease in Irish children was similar to that in England and Wales [8] with 36% and 35% respectively of all Hib disease occurring in children under 1 year. In contrast the native American Apache and Navajo populations experienced 40% and 30% respectively of all Hib infections in the first 6 months of life [14]. The general trend from international data is that the younger the occurrence of Hib disease the greater is its meningitic component.…”

“…Disease rates are higher in the United States (US) [1,9,10] than in western Europe [2,4,5,[11][12][13]. However, within the US, the native American and Alaskan native populations [10,14,15] experience particularly high Hib disease rates as do aboriginal children in Australia [6,16]. The reasons for such differences in Hib disease incidence are not fully understood but differing genetic susceptibilities among host populations have been suggested [17,18].…”