John V. Bennett

Nosocomial klebsiella infections: intestinal colonization as a reservoir.

Excerpt A prospective study of patients admitted to a hospital where there was endemic nosocomial infection with multidrug-resistant klebsiella was undertaken to evaluate the role of intestinal col...

Nationwide epidemic of septicemia caused by contaminated intravenous products. I. Epidemiologic and clinical features.

Between mid-1970 and April 1, 1971, Enterobacter cloacae or E. agglomerans septicemia developed in 378 patients in 25 American hospitals while they were receiving intravenous products manufactured by one company. Each of the hospitals noted a marked increase in the incidence of such septicemia during this period. Enterobacter agglomerans (formerly designated Erwinia, herbicola-lathyri group) was better known as a plant pathogen and had been a human blood pathogen only rarely in the past. Septicemia caused by E. cloacae had also been uncommon.

Effect of subclinical infection on maintaining immunity against measles in vaccinated children in West Africa

BACKGROUND Despite a high coverage with measles vaccines in parts of west Africa, epidemics of measles occur with reduced severity in an increasing proportion of older children who have been vaccinated. We examined the effect of exposure to natural measles on immunity in vaccinated children. METHODS Our study was carried out in 1992 during an epidemic of measles in Niakhar, a rural area of Senegal with about 27,000 inhabitants who mostly live in compounds that include several households; within each household people live in different huts. Vaccine coverage in Niakhar was 81% at the time of our study. We measured haemagglutinin-inhibiting antibody at exposure and twice thereafter (after 4-5 weeks and at 6 months) in 36 vaccinated and 87 unvaccinated children. The frequency of measles and subclinical measles--defined as a four-fold or greater rise in antibody titre without clinical signs or symptoms--was related to intensity of exposure according to whether the index case was in the same hut, household, or compound. FINDINGS Clinical measles occurred in 20 (56%) of 36 unvaccinated children and in one (1%) of 87 vaccinated children. Subclinical measles occurred in 39 (45%) of 86 vaccinated children who were exposed to measles and in four (25%) of 16 unvaccinated children. The frequency was inversely related to pre-exposure antibody concentration (p<0.001 for trend) and directly related to intensity of exposure (p=0.002 for trend). Antibody concentrations in subclinical cases increased on average by 45-fold and remained raised for at least 6 months. INTERPRETATION Increased antibody titre after subclinical measles may be common in vaccinated children in West Africa where the intensity of exposure is high. As measles vaccination coverage increases, the circulation of wild measles will decrease, and vaccine-induced antibody is less likely to be boosted. Thus, new epidemics, albeit milder in form, may occur in vaccinated areas which should be recognised in campaigns to eradicate measles.

A simultaneous outbreak of meningococcal and influenza infections.

Abstract During a nine-day period in January, 1968, 11 cases of systemic Group B, sulfonamide-resistant Neisseria meningitidis infections with three deaths occurred among 55 elderly women confined ...

Response to different measles vaccine strains given by aerosol and subcutaneous routes to schoolchildren: a randomised trial

BACKGROUND More than one dose of measles vaccine is necessary for the sustained control of measles. The aerosol route is thought to be more immunogenic for booster doses than traditional subcutaneous injections, so we did a randomised comparative trial of aerosol and subcutaneous measles vaccines in South African schoolchildren. METHODS 4327 schoolchildren (aged 5-14 years), assigned by block randomisation of classrooms, received standard titre doses of either Schwarz or Edmonston-Zagreb measles vaccines subcutaneously or by aerosol. Blood samples for antibody assay were collected before vaccination, at 1 month, and 1 year after vaccination. The main endpoints (antibody titres at 1 month and 1 year) were compared between groups. FINDINGS 992 children had antibody titre data available for all timepoints. 14 (3.6%) of 385 children who received Edmonston-Zagreb vaccine by aerosol were seronegative 1 year after vaccination, compared with 28 (8.6%) of 326 children who received Edmonston-Zagreb subcutaneous vaccine and 39 (13.9%) of 281 children who received Schwarz subcutaneous vaccine. At 1 month, 326 (84.7%) children who received aerosol Edmonston-Zagreb vaccine had seroconverted, compared with 257 (78.8%) who received subcutaneous Edmonston-Zagreb vaccine and 176 (62.6%) who received subcutaneous Schwarz vaccine. At 1 month, only 116 (22.7%) of 511 children in the Schwarz aerosol group had seroconverted; this aerosol vaccine had no detectable potency after 2 min of nebulisation. There were no serious side-effects: about 5% of children in each group had a rash within 2 weeks of vaccination. INTERPRETATION An aerosol vaccination method that uses currently available devices and a suitably stable vaccine is effective and acceptable. This form of delivery is adaptable to mass campaigns, avoids the risks associated with injections, and could help measles eradication.

Gram-Negative-Rod Bacteremia

The incidence of gram-negative-rod bacteremia has increased during the past two decades.1 A recent paper estimated that there may be as many as 300,000 cases per year in the United States, with app...

Serologic status and measles attack rates among vaccinated and unvaccinated children in rural Senegal

During a measles vaccine trial in a rural area of Senegal, antibody status was examined within 10 days of exposure for 228 previously vaccinated and 313 unvaccinated children more than 12 months old who were exposed to measles at home. Thirty-six percent of the children developed clinical measles, the clinical diagnosis being confirmed for 135 of the 137 children from whom 2 blood samples were collected. Vaccine efficacy was 90% (95% confidence interval, 83 to 94%). The hemagglutinin-inhibiting antibodies (HI) or plaque neutralizing antibodies (PN) assays were equally efficient in predicting susceptibility and protection against measles. Vaccinated children who had no detectable HI or PN antibodies at exposure had significant protection against measles compared with seronegative unvaccinated children (HI vaccine efficacy, 49% (95% confidence interval, 21 to 68%); PN vaccine efficacy, 43% (95% confidence interval, 12 to 62%)). The attack rate was high for children with a titer of 40 to 125 mIU) 67% (4 of 6) of those with a positive hemagglutinin-inhibiting antibody test and 36% (13 of 36) of those with a positive PN test developed measles. Attack rates among children with HI or PN titers above 125 mIU were 2% (6 of 295) and 3% (7 of 258), respectively. Because titers of ≥120 mIU have been found to offer little protection in another study, this antibody level may be the best screening value for assessing susceptibility and protection against measles. However, it should be noted that many seronegative vaccinated children are protected against measles infection.

Aerosolized measles and measles-rubella vaccines induce better measles antibody booster responses than injected vaccines: randomized trials in Mexican schoolchildren.

OBJECTIVE To compare antibody responses and side-effects of aerosolized and injected measles vaccines after revaccination of children enrolling in elementary schools. METHODS Vaccines for measles (Edmonston-Zagreb) or measles-rubella (Edmonston-Zagreb with RA27/3) were given by aerosol or injection to four groups of children. An additional group received Schwarz measles vaccine by injection. These five groups received vaccines in usual standard titre doses. A sixth group received only 1000 plaque-forming units of Edmonston-Zagreb vaccine by aerosol. The groups were randomized by school. Concentrations of neutralizing antibodies were determined in blood specimens taken at baseline and four months after vaccination from randomized subgroups (n = 28-31) of children in each group. FINDINGS After baseline antibody titres were controlled for, the frequencies of fourfold or greater increases in neutralizing antibodies did not differ significantly between the three groups that received vaccine by aerosol (range 52%-64%), but they were significantly higher than those for the three groups that received injected vaccine (range 4%-23%). Mean increases in titres and post-vaccination geometric mean titres paralleled these findings. Fewer side-effects were noted after aerosol than injection administration of vaccine. CONCLUSION Immunogenicity of measles vaccine when administered by aerosol is superior to that when the vaccine is given by injection. This advantage persists with aerosolized doses less than or equal to one-fifth of usual injected doses. The efficacy and cost-effectiveness of measles vaccination by aerosol should be further evaluated in mass campaigns.

Guidelines for infection control in intravenous therapy.

Abstract Infusion-associated septicemia is an appreciable hazard to the more than 8 million patients who receive intravenous therapy in U.S. hospitals each year. Rigorous infection control measures...

Dry powder inhalation as a potential delivery method for vaccines

Measles vaccine is administered to millions of children annually via a percutaneous injection. There are, however, compelling reasons to search for alternative routes of administration, especially in mass vaccination campaigns. Two key factors are (1) decreased stability of the vaccine upon reconstitution and, (2) the potential risks of contamination associated with needles. Dura has developed a unique inhaler that can deliver a powder dose via the pulmonary route for local or systemic action. The breath-actuated Spiros inhaler uses electromechanical energy to aerosolize and deliver a consistent dose over a wide range of inspiratory flow rates. To achieve alveolar (deep lung) deposition for subsequent systemic absorption, dry-powder vaccine is size reduced to a mass median diameter between 1 and 5 microns. Small vaccine particles are blended with an inert carrier to improve dispersion. Measles vaccine formulated as a powder blend may be more thermostable than existing reconstituted formulations. The Spiros technology is available in three powder storage platforms. Two of these formats are designed specifically for moisture and/or light sensitive compounds and may be particularly suitable for delivery of measles vaccines in mass campaigns because their design (1) eliminates the need for powder reconstitution, and (2) reduces the risk of contamination.