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Haemophilus influenzae type b disease in Alaskan Eskimos is characterized by greatly increased disease incidence at younger ages. This suggests that Eskimo infants have increased exposure to the disease. Exposure was studied in 1982-1983 in children less than age three years who lived in four Eskimo villages, as well as in a random sample of their family members (354 people from 132 households). During a 12-month period, up to four pharyngeal cultures and two serum specimens were obtained from each participant. Colonization with H. influenzae type b was relatively uncommon (overall 2.5% of cultures, 6.8% of individuals) and was not associated with age, sex, season, or prior incidence of disease in the village. Biotyping and outer-membrane-protein typing of H. influenzae type b isolates revealed homogeneity within villages, with differences between villages. Matched sera revealed a significant decline in H. influenzae type b capsular antibody in the course of the study year. However, pharyngeal carriage of H. influenzae type b was associated with increases in antibody for carriers and members of their households. Antibody levels were positively associated with age. Only one case of H. influenzae type b disease developed during the study. Low carriage of H. influenzae type b was coincident with low incidence of disease and declining levels of capsular antibody in these villages. Mechanisms for increased exposure which would not be reflected in high carriage rates may exist for these young children.

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A 1960-62 study of southwestern Alaskan Eskimos documented an infant mortality rate--102.6 deaths per 1,000 live births--that was four times greater than that of U.S. whites. In 1980-81, 20 years after the original study, a similar cohort was identified in this population so that changes in infant mortality and other birth characteristics could be examined. Average birth weight and the amount of prenatal care received by the mothers increased from 1960 to 1980. Birth weight and prenatal visits were positively correlated. Results of the followup also revealed a 1980-81 infant mortality rate--17.1 deaths per 1,000 live births--that was less than a fifth of the 1960-62 rate and no longer significantly different from the national rate. Major changes associated with the decrease in mortality during the first 28 days of life (neonatal mortality) were a significant increase in the proportion of infants born in hospitals and an associated decrease in the number of deaths of infants weighing less than 2,500 grams at birth. The reduction in mortality during the rest of the first year of life was related to a decrease in deaths due to infectious diseases, particularly measles and pertussis. Changes in infant mortality reflect the increased availability of health care in this region, improved immunization programs, and the establishment of the Bethel Prematernal Home in Bethel, AK.

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In a previous study we demonstrated that Alaskan Eskimos had the highest endemic incidence of invasive Haemophilus influenzae type b (Hib) disease. In 1980 we established a prospective surveillance program for all invasive Hib disease throughout Alaska to characterize additional epidemiological features of disease in Native Alaskans to plan for a vaccine efficacy trial and define the epidemiology of Hib disease in all population groups in the state. For the three-year period, 1980-1982, 287 confirmed episodes of invasive Hib disease occurred. For children less than five years of age, the incidences for Eskimos, Indians, and non-Natives were 705, 401, and 129 cases per 100,000 population, respectively. The Native population represents only 16% of the population of Alaska but has 51% of all invasive Hib disease. Disease differed significantly among Eskimos, Indians, and non-Natives with regard to risk, age of onset, disease type, antibiotic susceptibility of strains, and regional incidence, but mortality and seasonal occurrence were similar. For Native Alaskans the cumulative Hib disease risk for the first two years of life was 4% (range, 1%-7% by region). This high endemic disease risk, concentrated in the first two years of life, provides a unique opportunity to prospectively evaluate the protective efficacy of a vaccine in a randomized, blinded, and placebo-controlled trial. Such a trial was initiated in December 1984.

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During 1971-77 the incidence of bacterial meningitis among Alaskan Eskimos was 84.4 cases per 100 000 population per year, which is more than 10 times that for most other U.S. populations. Haemophilus influenzae (HI) accounted for 68% of meningitis cases. The average annual incidence of HI disease per 100 000 children below 5 years of age was 409 for patients with meningitis only and 491 for patients with all systemic HI disease. Children with HI meningitis in Alaska tended to be younger than those in other U.S. populations, 98% of the children affected being less than 18 months of age. The risk for all HI disease was 2.4% during the first year of life. The spectrum of HI disease in Alaska differs from that in other populations in that no patient had epiglottitis and 5% of children had recurrent HI disease. Alaskan newborns and children over 4 years old had HI anticapsular antibody titres that were nearly thrice those for children of similar ages in other U.S. populations (p less than 0.005). The pharyngeal carriage of HI type b (5%) and the rectal carriage of Escherichia coli K100 (2%), an organism with a capsule antigenically similar to HI type b, did not differ from those in other populations. The high incidence of disease almost exclusively in the very young and the early development of antibody in this population suggest that the high rate of disease is due to early exposure to HI type b rather than to an unusual susceptibility to HI type b.

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A narcissus alkaloid, pretazettine hydrochloride (PTZ), has been shown to be active against Ehrlich ascites carcinoma. The Ehrlich cells are more sensitive to PTZ in DBA/2 mice than in Swiss mice. The therapeutic activity of the individual standard drugs in ABC (adriamycin, BCNU, and cyclophosphamide) regimen against Ehrlich ascites carcinoma has been increased remarkably by the adjuvant therapy of PTZ following the preliminary use of standard drugs. The independent inhibitory action of PTZ on cellular protein synthesis in the presence of the DNA-binding agent has been demonstrated in KB-cell cultures. Adriamycin-pretreated KB cells are found to be more sensitive to PTZ than nontreated cells.

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Six cases of hepatitis B-associated vasculitis occurred during a four-year period in Eskimos living in southwest Alaska, an area hyperendemic for hepatitis B. All showed positive results in tests for hepatitis B surface antigen (HBsAg), and all five patients tested for hepatitis B e antigen (HBeAg) showed positive values. Two patients died of the disease. Of three who recovered, two had positive values for HBsAg and HBeAg when tested two years later. In the villages of four patients, the prevalence of hepatitis B virus (HBV) infection ranged from 18.2% to 73.1%. Serological evidence of HBsAg was found in 22% and antibody to HBsAg (anti-HBs) in 30% of close relatives of the patients. Two patients had no previous serological evidence of infection with HBV, indicating that vasculitis followed recent infection. The results provide epidemiologic evidence of the clinical association between HBV infection and vasculitis.

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Poststreptococcal acute glomerulonephritis often follows impetigo and can occur in epidemics. From 1975 through 1977, an epidemic of poststreptococcal acute glomerulonephritis occurred in Alaska. Fifty children required hospitalization, while 25 less seriously ill children were treated as outpatients. Sixty-seven percent of these 75 children had direct evidence of recent skin infections. Serotypes 49-14 and NT-14 were the most common streptococcal isolates. In villages in the epidemic area, approximately 15% of children had impetigo and more than 60% of lesions cultured were positive for group A streptococci. Impetigo rates in the epidemic area were similar to those found in nonepidemic areas. However, the introduction of the nephritogenic streptococcal serotypes not recently present in this population apparently led to the development of the epidemic.

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A narcissus alkaloid, pretazettine hydrochloride (PTZ) has been shown to be active against spontaneous AKR leukemia. The long-term treatment with PTZ begining at 5--7 months of age of a group of AKR mice containing 10--20% of advanced leukemic mice significantly prolonged the life span of the group. The therapeutic effectiveness of PTZ has been compared with several standard antileukemic drugs. PTZ decreased the AKR virus titer in the circulating blood of mice and its antiviral activity in AKR virus infected NIH/3T3 cells has been confirmed by XC assay.

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