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Objective. To evaluate the effectiveness in low birth weight (LBW) infants of the currently recommended immunization schedule for conjugated Haemophilus influenzae type b (HIB) vaccine. Methods. We quantified antibody responses in 36 preterm infants with a mean birth weight of 1060 g and a mean gestational age of 28 weeks. Infants were immunized with 0.5 mL of HIB vaccine at 2 and 4 months' postnatal age. Specific HIB antibodies were quantified on cord blood, immediately before each immunization and 2 months after the last immunization. Results. Even though the geometric mean titers increased significantly during the study period, they were still markedly lower than values reported in term infants. After the second immunization, only 24 infants (67%) attained antibody concentrations of more than 0.25 µg/mL, defined as seropositivity. Also, only 53% of infants achieved antibody concentrations of more than 1.0 µg/mL compared with 92% as reported in term infants. Stepwise logistic regression identified gestational age of 27 weeks or less and the amount of intravenous immunoglobulin received as the significant variables influencing the antibody response after the first immunization. The incidence of side effects was negligible. Conclusions. We conclude that LBW infants, and especially those born at 27 or less weeks' gestation, do not respond as effectively to the HIB vaccine. We speculate that reevaluation of the current immunization schedule may be required for very LBW infants.

A total of 44 children with acute lymphoblastic leukemia were immunized against chickenpox with the Oka/Merck strain live attenuated varicella vaccine. Of these children, 24 continued oral chemotherapy with 6-mercaptopurine during the immunization period and 20 had suspension of all chemotherapy for 1 week before and 1 week after the vaccine. Seroconversion, as determined by the detection of fluorescent antibody to membrane antigens, occurred in 91% and did not differ between patients continuing 6-mercaptopurine from those in whom chemotherapy was suspended. Fever and/or rash occurred in less than one third of vaccinated children. Unexpected reactions occurred in two vaccinated children, one from each group, both of whom had low absolute lymphocyte counts (

Four hundred nineteen children and adolescents immunized with live varicella vaccine 4-6 years earlier were enrolled in a study to evaluate the safety and immune response to a booster dose containing approximately 3300 pfu of virus. Of the subjects, 99% (414/419) maintained antibody to varicella zoster virus (VZV) with a geometric mean titer of 25.7 and mean stimulation index (SI) for VZV-specific lymphoproliferation response of 40.3 +/- 5.3 (SE). Some 7-10 days after the booster immunization, seropositivity rates increased to 100% (302/302), and GMT was 143.6 (anamnestic response). At 6 weeks after the booster inoculation, a subset of subjects had 100% seropositivity (74/74) with a GMT of 218.8 and an SI of 58.6. After 3 months, seropositivity was 100% (358/358), GMT was 119.0, and SI was 61.4.

Five hundred and fifty-seven infants received either an acellular pertussis (DTaP) vaccine containing pertussis toxoid (PT), filamentous hemagglutinin (FHA) and pertactin (PRN) or one of two commercially available whole-cell pertussis (DTP) vaccines at 2, 4 and 6 months. One month after the third immunization, IgG antibody values to pertussis toxoid, filamentous hemagglutinin and PRN were significantly greater following DTaP than either DTP (P

Pretreatment of normal adult peripheral blood mononuclear cells with interferon-α (IFN-α) resulted in enhanced natural killing (NK) of varicella-zoster virus (VZV)-infected and uninfected target ce...

Extract: Two live “attenuated” respiratory syncytial virus (RSV) vaccines were administered intranasally and by aerosol in placebo-controlled trials among asthmatic children hospitalized at National Jewish Hospital and Research Center (NJH). The first vaccine, a 26° -adapted RSV vaccine, was given to 28 children, and a placebo control was given to 25. Twenty-one of 28 vaccinees (75%) had “takes,” as judged by virus shedding and/or rises in serum antibody and/or rises in nasal secretion neutralizing activity. No excess in wheezing was attributable to the vaccine administration, although there was a high background level of acute respiratory symptoms in both vaccinees and control subjects. In an outbreak of natural RSV infection which occurred some months after the vaccine was given, there was some evidence that those who received the vaccine less than 4 months before exposure to wild virus were protected against reinfection. Protection was not evident when this interval was greater than 4 months. The second vaccine, a temperature-sensitive mutant strain (ts-1), was administered to 22 children, and placebo to 21. Thirteen children (59%) had “takes.” In vaccinees under 6 years of age, 7 of 7 had “takes.” Again, no excess wheezing was seen in vaccinees as compared with control subjects, although there was some evidence that upper respiratory symptoms were more frequent in younger vaccinees. Four of 10 vaccinees shed virus with temperature-sensitive characteristics somewhat different from those of the vaccine strain. Vaccine virus was demonstrated to spread to uninoculated or placebo control children. Natural RSV challenge did not occur during the period of study. Speculation: One of two live “attenuated” RSV vaccines may have produced a brief period of protection against natural infection. This finding offers hope that such live vaccines might prevent disease in selected children over a critical time period, such as infants for the 1st year of life, or allergic or asthmatic children during periods of epidemic prevalence. Asthmatic children did not appear to develop symptoms of wheezing after attenuated RSV infection. This finding suggests that the mechanism of wheezing in asthmatic children with RSV infection may be dependent on, among other factors, the virulence of the virus strain (perhaps its capacity to replicate in and, possibly, invade the lower respiratory tract), rather than on an allergic response to antigens introduced into, and limited to, the upper airway. In view of the spread of the ts-1 vaccine and its apparent loss of temperature sensitivity in some vaccinees, the vaccine may have had the potential for reversion to virulence and hence initiation of epidemic disease. These characteristics are undesirable in live respiratory virus vaccines and should, if possible, be avoided in the development of future such vaccines.

The elimination pharmacokinetics of tobramycin sulfate was studied in 25 newborn infants of birth weight 0.7 to 4.7 kg during 31 treatment episodes. The peak serum concentrations after a 2.5 mg/kg dose were usually within the therapeutic range of 5 to 10 micrograms/ml; however, the serum predose trough values were elevated above the theoretical safe limit of 2 micrograms/ml. Because of the prolonged serum elimination half-lives, a calculated extended dosage interval, sometimes greater than 24 hours, was necessary to obtain a predose trough of less than or equal to 2 micrograms/ml. The serum elimination half-lives inversely correlated with gestational age, extrauterine age, birth weight, and creatinine clearance. The very low ratio of tobramycin renal clearance to creatinine renal clearance was virtually constant and indicated a probable tubular reabsorption of tobramycin. A general dosage schedule based on birth weight was derived from the data. An alternative formula was derived to enable prediction of the tobramycin elimination half-life based on a combination of birth weight, gestational age, and extrauterine age for an infant younger than 7 days of age.

Ninety-one healthy children were immunized with one of three preparations of the OKA strain of live attenuated varicella zoster virus in order to gain sufficient information on safety and immunogenicity to justify vaccine studies in immunosuppressed children. The OKA-Biken vaccine was studied in a dose response trial. Two additional clinical trails were conducted with the OKA strain that was further passaged; a frozen aqueous (OKA-RIT-Aq) form and a lyophilized (OKA-RIT-Ly) form were tested. With each of these vaccines clinical reactivity was minimal and virus shedding, viremia, and transmission of the vaccine virus were absent. Excellent seroconversion rates of 100 and 94% were induced with approximately 500 pfu of OKA-Biken and OKA-RIT-Ly vaccine, respectively. A lower seroconversion rate was noted for OKA-RIT-Aq, presumably on the basis of defective individual vials. Diluted OKA-Biken vaccine induced less seroconversion but even the 5 pfu dose produced antibody responses in 81% of the vaccinees. In vitro specific cellular immune responses to varicella virus antigens were demonstrated in each group of vaccinees, including all but two of those vaccinees who failed to seroconvert. The data indicate that two preparations of the OKA strain are sufficiently safe and immunogenic in healthy children to support further studies in immunocompromised children.

The KMcC strain of live, attenuated varicella-zoster virus vaccine was studied in healthy children as a preliminary step toward varicella vaccine studies with this strain in children with leukemia. Forty-three children were immunized: 26 with the 40th passage vaccine and 17 with the 50th passage. Studies included surveillance for clinical reactivity, oropharyngeal excretion of vaccine virus, viruria, and viremia. Antibody responses were assayed by fluorescent antibody to membrance antigens and immune adherence hemagglutination. Cell-mediated immune responses were assayed by lymphocyte proliferation to varicella-zoster virus specific antigens. There was 100% seroconversion to the KMcC passage 40 and 50 vaccines (by fluorescent antibody to membrane antigen assay). Every child studied developed in vitro lymphocyte proliferation to varicella-zoster virus antigens. Papular skin lesions, probably vaccine related, occurred in 31% of the 40th passage vaccinees but in only 6% of the 50th passage vaccinees. The 50th passage KMcC strain vaccine is sufficiently immunogenic and safe to initiate clinical studies with leukemia patients.

We studied mononuclear cell (MNC)-mediated natural killing (NK) of varicella-zoster virus (VZV)-infected fibroblasts in normal children, children with VZV infections, and children with Hodgkin's disease. NK activity was tested in 18 hr 51Cr release assays. NK activity for adults was significantly higher than that for children 1-3 years old or 4-6 years old (p less than 0.05). Serological status did not affect NK activity. NK activity in normal children was not increased 4-6 weeks after immunization with varicella vaccine. Seven normal children with natural varicella showed significantly higher NK activity against VZV-infected and uninfected targets. Eight immunosuppressed children with herpes zoster showed significantly reduced NK activity within 72 hours of the onset of herpes zoster. However, their NK activity rose to the normal level one to two weeks later. Children with Hodgkin's disease had low NK activity. These results suggested that NK cells might play an initial defensive role in VZV infections, and that low NK activity in immunocompromised hosts might contribute to their high incidence of herpes zoster.

Ninety children, ages 7 to 13 years, who had received Edmonston B live measles vaccine and gamma globulin simultaneously 6 to 9 years ago were reimmunized and their antibody responses were examined. Twenty-three of the 90 children had no pre-reimmunization hemagglutination-inhibiting antibody and had a primary response to “reimmunization”. All of these primary responders were less than a year of age at the time of initial immunization.

Antibody responses of two doses of a bivalent influenza vaccine containing A/Victoria/75 (A/Vic/75) and A/New Jersey/76 (A/NJ/76) viral antigens were studied in 22 children receiving maintenance chemotherapy for acute lymphoblastic leukemia (ALL), 16 children no longer receiving therapy for ALL, and 50 sibling controls. Before immunization, the three groups showed no difference in titer of antibody to either antigen. After the first immunization, children off therapy showed significantly higher titers to A/NJ/76 than did either sibling controls of children receiving therapy (P less than 0.01). After the second immunization, children off therapy showed significantly higher antibody titers to both antigens than did children receiving therapy or controls (P less than 0.01 for both A/NJ/76 and A/Vic/75). Antibody titers of children receiving therapy were not significantly different from those of controls. A year later, there were no significant differences in antibody titers among the groups. Thus, children with ALL who are receiving chemotherapy respond normally to two doses of influenza vaccine, whereas children off therapy manifest abnormally high titers of antibody to both influenza virus antigens.

1. Vichinsky EP, and Lubin BH: Sickle cell anemia and related hemoglobinopathies, Pediatr Clin North Am 27:429, 1980. 2. Hook EW, Campbell CG, Weens HS, and Cooper GR: Sahnonella osleomyelitis in patients with sickle cell anemia, N Engl J Med 257:403, 1957. 3. Hughes JG, and Carroll DS: Salmonella osteomyelitis complicating sickle cell disease, Pediatrics 19:184, t957. 4. Diggs LW: Bone and joint lesions in sickle cell disease, Clin Orthop 52:119, 1967. 5. Barrett-Connor E: Bacterial infection and sickle cell anemia: An analysis of 250 infections in 166 patients and a review of the literature, Medicine 50:97, 1971. 6. Engh CA, Hughes JL, Abrams RC, and Bowerman JW: Osteomyelitis in the patient with sickle cell disease: Diagnosis and management, J Bone Joint Surg 53-A:1, 1971. 7. Dich VQ, Nelson JD, and Haltalin KC: Osteomyelltis in infants and children: A review of 163 cases, Am J Dis Child 129:1273, 1975. 8. Seeler RA, and Jacobs NM: Pyogenic infections in chiidren with sickle hemoglobinopathy, J PEDIA'i'R 90:161, 1977 (letter). 9. Sennara H, and Gorry F: Orthopedic aspects of sickle cell anemia and allied hemoglobinopathies, Clin Orthop 130:154, 1978. 10. Adeyokunnu AA, and Hendrickse RG: Salmonella osteomyelitis in childhood: A report of 63 cases seen in Nigerian children of whom 57 had sickle cell anaemia, Arch Dis Child 55:175, 1980.

Serial sera from 50 marrow transplant recipients were examined for their spectra and titers of antibodies to EBV-specific antigens. Immediately before or after transplant, blood products passively transferred antibodies to EB viral capsid antigen (VCA) and EBV nuclear antigen (EBNA). In most recipients, passively-transferred antibodies were replaced by endogenous antibodies regardless of whether donor or recipient had EBV antibodies before transplantation. Commencement or resumption of endogenous EBV antibody production was not associated with signs of infectious mononucleosis or heterophil antibody responses. Antibodies to VCA rose to abnormally high titers, followed successively by antibody to early antigens (EA), and disproportionately low levels of anti-EBNA. Unusually high anti-VCA and anti-EA levels persisted when tests of immune function returned to normal. Antibodies to other herpes group viruses showed no consistent changes. We conclude that (1) EBV does not cause significant clinical problems in marrow transplant recipients; (2) persistent EBV infection can become established or reestablished in the presence of antibodies to EBV; (3) marrow transplant recipients show the same exaggerated immune response to EBV as other immunodeficient patients; and (4) the pattern of EBV-specific antibodies may be a more sensitive measure of defective cell-mediated immunity than most conventional tests of immune function.

Mouse cytomegalovirus (CMV) was rapidly and completely inactivated at 37 C by formalin diluted 1:4,000. Of 18 mice that received two doses of inactivated mouse CMV, 16 survived challenge with 250% lethal doses of mouse CMV; one of 11 mice receiving two doses of a control preparation survived the challenge (P < 0.005). After challenge with live virus, recognizable morbidity occurred in only four of 16 recipients of inactivated mouse CMV, but the virus was recovered from the salivary glands of 15 animals. Mice with reciprocal prechallenge titers of neutralizing antibody of < 4 demonstrated significantly higher morbidity and mortality than mice with higher antibody titers. Administration of inactivated mouse CMV did not depress responsiveness of spleen cells to phytohemagglutinin. Most mice immunized with inactivated virus developed only mild or subclinical infections after challenge with lethal doses of mouse CMV.

Summary An infant is described who had severe intestinal loss of protein and died of polypoid adenomatosis of the entire gastrointestinal tract from the esophagogastric junction to the anus. Consideration of possible diagnostic entities reveals that this was a sporadic case not fitting into the more common syndromes.

Persistent colonization of the respiratory tract with μs. aerug. is a major problem in children with cystic fibrosis (CF). Because gentamicin penetration of CF sputum is inadequate after parenteral administration, we undertook an investigation of the safety and efficacy of gentamicin aerosol. Nine CF children (5F, 4M) ages 6-15 years with moderately severe disease were studied. Following baseline pulmonary and microbial studies, each child received 40 mg of gentamicin sulfate by nebulization three times daily for one week. Gentamicin disposition and pulmonary function were studied initially and at the end of the treatment program. No adverse effects from the treatment were observed. Peak sputum concentrations of gentamicin varied from 3.6 to 18.5 mcg/ml after one dose to 6.4 to 33 mcg/ml after one week of therapy. Peak blood concentrations ranged from 0 to 0.35 mcg/ml initially and were somewhat higher at the end of the treatment program. Urinary concentrations were insignificant. The mean clearance of gentamicin from the sputum was 51 ml/min/1.73 m2 (6 pts). Microbial studies in five patients demonstrated a striking decrease in pseudomonas colony counts. No strains developed resistance to gentamicin. Pulmonary function tests improved in 5 patients, showed no change in 3, and diminished in 1, perhaps in association with a clinical URI. All the children showed marked clinical improvement. These results provide a rationale for, and strongly warrant, a clinical trial of aerosolized gentamicin in CF patients.

To determine if children with acute lymohoblastic leukemia (ALL) can mount a primary response to immunization with a new antigen and a secondary response to a known antigen, 39 children with ALL and 51 sibling controls received 2 doses of bivalent split-product influenza vaccine, A Victoria/75, A New Jersey/76 (A/Vic, A/NJ). Before immunization 90% of patients and controls had hemagglutination inhibiting antibody (HAI) to A/Vic of ≥ 1:8; none showed HAI antibodies to A/NJ. Four weeks after the first dose 74% of patients and controls showed at least a 4-fold rise in HAI titer to A/Vic. Only 48% of patients on chemotherapy responded to the first A/NJ immunization compared to 68% of controls and 89% of patients off therapy. Following the second dose, 86% of patients on therapy demonstrated at least a 4-fold rise in titers to both viruses with geometric mean titers of 1:68 to A/Vic and 1:43 to A/NJ. Patients who were off therapy developed higher HAI titers than controls. The results demonstrate that patients receiving chemotherapy can produce anti-influenza antibody in response to immunization with either an old antigen or a new antigen. Responses to the new antigen in patients on chemotherapy are more sluggish than those of controls but adequate antibody levels are achieved with booster immunization.

Beginning in 1979, OKA and KMcC strains of varicella zoster virus (VZV) vaccine were administered to 369 healthy seronegative children in a sequence of ten comparative clinical trials. Postimmunization clinical reactivity was minimal with the OKA vaccines but was unacceptably high (32%) with the KMcC passage-40 vaccine. Ninety-three percent to 100% immunogenicity was noted by fluorescent antibody assay and in vitro lymphocyte proliferation to VZV antigens. Follow-up studies demonstrated persistence of antibody and in vitro lymphocyte proliferation responses and protection or modification of infection nine to 48 months after immunization. Only five episodes of mild varicella occurred in children in whom seroconversion had occurred. These episodes were noted after at least 281 known varicella exposures. Vaccine virus reactivation as zoster had not occurred in any child.

Experiences With A Multiple Resistant Klebsiella pneumonias In An Infant Intensive Care Unit

• We reviewed the records of 96 children hospitalized with varicella from July 1, 1975 to June 30, 1980. Eighty-one were immunologically normal and 15 were immunocompromised on the basis of neoplasia, immunosuppressive therapy, or genetic disease. These children experienced 106 complications including viral dissemination-encephalitis (44), bacterial infection (25), Reye's syndrome (17), unusual cutaneous lesions (eight), drug overdose (five), diabetic ketoacidosis (two), neonatal infection (two), dehydration (two), and exacerbation of preexisting nephrosis (one). The length of hospitalization varied from one to 38 days, with a median of five days. There were ten deaths: of Reye's syndrome (seven), of varicella pneumonia (one), of neonatal varicella (one), and of a ruptured mycotic aneurysm secondary to septicemia (one). This review demonstrates (1) a substantial occurrence of life-threatening complications of varicella in childhood, and (2) a need for. prospective epidemiologic data on the incidence of complications to determine the scope and extent of varicella vaccination. (Am J Dis Child1981;135:896-899)