A case-control study of risk factors for Haemophilus influenzae type B disease in Navajo children.

To understand the potential risk factors and protective factors for invasive Haemophilus influenzae type b (Hib) disease, we conducted a case-control study among Navajo children less than two years of age resident on the Navajo Nation. We analyzed household interview data for 60 cases that occurred between August 1988 and February 1991, and for 116 controls matched by age, gender, and geographic location. The Hib vaccine recipients were excluded from the analyses. Conditional logistic regression models were fit to examine many variables relating to social and environmental conditions. Risk factors determined to be important were never breast fed (odds ratio [OR] = 3.55, 95% confidence interval [CI] = 1.52, 8.26), shared care with more than one child less than two years of age (OR = 2.32, 95% CI = 0.91, 5.96); wood heating (OR = 2.14, 95% CI = 0.91, 5.05); rodents in the home (OR = 8.18, 95% CI = 0.83, 80.7); and any livestock near the home (OR = 2.18, 95% CI = 0.94, 5.04).

Immunogenicity, safety and tolerability of varying doses and regimens of inactivated hepatitis A virus vaccine in Navajo children.

The Navajo are known to be at high risk for hepatitis A virus (HAV) infection. This study investigated the safety and immunogenicity of an investigational, alum-adjuvanted, formalin-inactivated HAV vaccine (VAQTA) developed by Merck Research Laboratories in Navajo children. One hundred two of 212 children, ages 4 to 12 years, were HAV-seronegative (< 10 mIU/ml by an enhanced sensitivity modification of the HAVAB; Abbott). Ninety of these children received the HAV vaccine. Study participants were given vaccines containing various viral protein concentrations: Group A (n = 18), 6 units; Group B (n = 36), 13 units; and Group C (n = 36), 25 units HAV protein (1 unit approximately 1 ng viral protein antigen). Three-dose (0, 8, 24 weeks) and two-dose (0, 24 weeks) regimens were compared in subgroups within B and C. The vaccine was well-tolerated and there were no serious adverse reactions; no vaccinee developed hepatitis A. After 1 dose 82 to 100% of children seroconverted (> or = 10 mIU/ml, modified HAVAB; Abbott) and 100% seroconverted after 2 doses. After 1 dose the geometric mean titer for antibody was: Group A, 22 mIU/ml; Group B, 18 mIU/ml; and Group C, 38 mIU/ml. After 3 doses geometric mean titers increased to 10,106 mIU/ml in Group A, 7258 mIU/ml in Group B and 11,856 mIU/ml in Group C. Further field studies are indicated to evaluate its use in high risk populations, such as the Navajo.

Antibody response of Navajo children primed with PRP-OMP vaccine to booster doses of PRP-OMP vs. HbOC vaccine.

We compared in 12- to 15-month-old American Indian infants the safety and immunogenicity of two licensed Haemophilus influenzae type b (Hib) conjugate vaccines, PRP-OMP (PedvaxHib) and HbOC (HibTITER), administered as booster vaccinations. All infants previously received PRP-OMP for their primary Hib vaccinations at 2 and 4 months of age. The geometric mean Hib antibody concentrations (microgram/ml) measured by radioactive antigen-binding assay for those receiving PRP-OMP (n = 17) or HbOC (n = 18) were 0.593 and 0.449, respectively, before boosting (P not significant) and 7.46 and 29.5 micrograms/ml, respectively, after boosting (P < 0.05). PRP-OMP recipients also had lower geometric mean IgG anti-Hib antibody concentrations than HbOC recipients (7.21 vs 28 micrograms/ml, P = 0.003) and lower bactericidal titers (3.18 vs. 15.4, not significant). We conclude that HbOC vaccine produced a significantly greater booster response than PRP-OMP vaccine when given at 12 to 15 months of age to children primed with two doses of PRP-OMP vaccine at 2 and 4 months of age.

Vaccination with Haemophilus influenzae type b meningococcal protein conjugate vaccine reduces oropharyngeal carriage of Haemophilus influenzae type b among American Indian children.

The effect of Haemophilus influenzae type b (Hib) meningococcal protein conjugate vaccine (Hib-OMPC; Merck, Sharp & Dohme) on oropharyngeal (OP) carriage of Hib was evaluated in Navajo and Apache Indian children, who are known to be at high risk for invasive Hib disease. We obtained 1423 OP swabs at well child visits from 1321 children 3 months to 4 years of age: 293 of the swabs were obtained from children before the administration of any Hib-OMPC; 1119 were taken after the primary vaccination series; and 11 after the booster dose. Swabs were tested for the presence of Hib capsular polysaccharide antigen by enzyme-linked immunosorbent assay. Forty of 1423 swabs were positive for Hib. Among the 40 positive swabs 5 (13%) were obtained from children who had received Hib-OMPC vaccine appropriate for age at swabbing, compared with 500 of 1383 (36%) of negative swabs. Children who were OP carriers of Hib were older than noncarriers (mean age, 13 and 9 months, respectively) and a greater proportion of carriers (48%) had symptoms of respiratory infection at the time of swabbing than noncarriers (30%). These variables were significantly related to increased risk of OP carriage of Hib when incorporated jointly in a logistic regression model: not vaccinated according to age (odds ratio 2.7, 95% confidence interval 1.00 to 7.05); increase of age in months (odds ratio 1.1, 95% confidence interval 1.02-1.10); and respiratory infection symptoms present (odds ratio 2.0, 95% confidence interval 1.06-3.77). Thus besides preventing invasive Hib disease, appropriate vaccination with Hib-OMPC appears to reduce OP carriage of Hib.

Prevention of Haemophilus influenzae type b infections in Apache and Navajo children.

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.

The efficacy in Navajo infants of a conjugate vaccine consisting of Haemophilus influenzae type b polysaccharide and Neisseria meningitidis outer-membrane protein complex.

BACKGROUND AND METHODS: Several conjugate vaccines against Haemophilus influenzae type b have been developed in the search for one that induces protection even in young infants. We evaluated the safety and efficacy of a conjugate vaccine that links the H. influenzae type b capsular polysaccharide to the outer-membrane protein complex (OMPC) of Neisseria meningitidis serogroup B. We conducted a double-blind, placebo, controlled trial in Navajo infants, who are at high risk for systemic infections caused by H. influenzae type b. The infants were randomly assigned to receive the first dose of vaccine or placebo at 42 to 90 days of age and the second at 70 to 146 days of age. RESULTS: Of the infants in the trial, 2588 were assigned to receive the vaccine and 2602 to receive placebo. The mean follow-up was 269 days in the vaccine group and 267 days in the placebo group. Before the age of 18 months, there was 1 systemic H. influenzae type b infection in the vaccine group, as compared with 22 in the placebo group (P less than 0.001; point estimate of efficacy, 95 percent; 95 percent confidence interval, 72 to 99 percent). Of the 22 H. influenzae type b infections in the placebo group, 13 were meningitis. Among the children who received both doses, there was 1 H. influenzae type b infection in the vaccine group (n = 2056) and 14 in the placebo group (n = 2105) (P less than 0.001; point estimate of efficacy, 93 percent; 95 percent confidence interval, 53 to 98 percent). The single infection in the vaccine group occurred at 15 1/2 months of age in an infant with osteomyelitis. Between the first and second doses there were no H. influenzae type b infections in the vaccine group and eight in the placebo group (P less than 0.005; point estimate of efficacy, 100 percent; 95 percent confidence interval, 41 to 100 percent). CONCLUSIONS: The H. influenzae type b OMPC vaccine, administered at 2 and 4 months of age, is safe and induces a high rate of protection against invasive disease caused by H. influenzae type b in infants under the age of 18 months. Protection begins after the first dose.

Accumulation of radioiodine in thiouracil-hyperplastic thyroids of chicks.

Kinetics of accumulation of radioiodine was studied in thyroids of chickens before, during, and following ingestion of 0.25% thiouracil (TU). After a latent period of about 5 days, weight of the thyroid gland increased, reaching its maximum (42 mg/100 g body wt) after 21 days of TU ingestion; thyroid weight decreased immediately on withdrawal of TU but tended to plateau at a higher level than that of controls. One-way clearance increased by day 4 of ingestion of TU and reached its peak early during hyperplasia; it very quickly reverted to a control level on withdrawal of TU. Exit-rate constant increased markedly during early hyperplasia and decreased to a level less than normal after withdrawal of TU. Concentration of 127I decreased by a factor of 18 by 2 wk of feeding TU; it increased to practically a normal level by 1 wk after withdrawal of TU.

Variations in plasma prolactin, thyroid hormones, gonadal steroids and growth hormone in turkeys during the induction of egg laying and moult by different photoperiods.

1. Concentrations of prolactin, growth hormone, testosterone, progesterone, thyroxine and triiodothyronine were measured in the blood plasma of female turkeys during successive periods of egg laying, a decline in lay, a moult induced by a short photoperiod (6 light: 18 dark) and a resumption of egg laying induced by a long photoperiod (16L:8D). 2. Concentrations of prolactin, growth hormone, testosterone and progesterone were higher in laying birds than in birds which were moulting or not laying. 3. The concentration of testosterone, but not of the other hormones studied, increased significantly during the period of profuse moult. 4. Concentrations of the thyroid hormones did not change with the varying physiological condition of the birds. However, the concentration of thyroxine was depressed by the long photoperiod.

Dietary iodine and accumulation of radioiodine in thyroids of chickens.

Groups of hatchling white leghorn cockerels were fed a basic, semisynthetic low-iodine diet to which various amounts of iodide were added: 0 up to 100 microgram I/g feed. Growth rates were unaffected by the range of dietary iodine content. A transitory goiter occurred only in the group fed the basic low-I diet. Half-life of 131I in the thyroid increased directly and fractional turnover rate inversely with increase of dietary iodine. Trichloroacetic acid-soluble iodine in serum did not accurately reflect variation of dietary iodine. However, effective clearance and binding rate constants did decrease proportionally to dietary iodine increase beyond the first 3-5 days. Concentration of iodine in thyroid was directly proportional to dietary iodine after 10 days. There was no consistent correlation between thyroxine or triiodothyronine and dietary iodine except in general terms of high and low dietary iodine groups. The avian thyroid exhibits great lability in adjusting functionally to a wide range of dietary iodine contents.

Dietary iodine and thyroidal iodide transport in chickens: organic binding blocked.

Experimental data concerning the increase in T/S [I-] (ratio of concentration of radioiodide in thyroid to that in serum) during equilibration after a single injection of radioidide were obtained from chickens in which protein binding of radioidide was inhibted by methimazole. Equilibration data were obtained from chickens fed a low-iodine diet (2 mo) as well as the low-iodine diet to which various amounts of NaI had been added. Experimental data were compared with productions based on the open two-compartmental model of Wollman and Reed (Am. J. Physiol. 196: 113-120, 1959). Thyroidal clearance (C/m) of radioiodide (the rate at which radioiodide is transferred from blood into the thyroid and equal to the radioiodide content of C microliter serum per minute) varied inversely to iodine content of feed. Exit rate constant (KTB, the fraction of thyroidal radioiodide transferred to serum per minute) was relatively more constant. The experimental data fitted the predictions from the model within experimental error. Thirty days of feeding the low-iodine diet was required before C/m stabilized at 50 microliter/min per mg and KTB at 0.065; stabilization of C/m and KTB occurred in 12 days with the highest iodine diet.

Thyroxine and triiodothyronine in blood after ingestion of iodinated casein by chicks.

White Leghorn cockerels were fed a broiler ration containing 0 (controls), 0.02 or 0.04% Protamone (iodinated casein) either continuously or for 10-14 days after which the 0.02% Protamone ration was switched to control or vice versa. Body growth rate was temporarily suppressed during the first 14 days of feeding 0.02% Protamone. Thyroid weight was promptly depressed during feeding of Protamone and increased more slowly when Protamone was removed from the feed. Only a fleeting increase in oxygen consumption rate was detectable in birds fed either 0.02 or 0.04% Protamone. Serum T4 and T3 promptly rose when Protamone was fed; continued feeding resulted in compensatory adjustments in secretion and perhaps peripheral metabolism of iodohormones within 2-3 days so that a level close to 200 ng. T3 or 2.5 mug T4/100 ml. serum was subsequently maintained.