IDCP SNAPSHOTS

May 2001 More Evidence that Pertussis Is Common in Adults A large study from Canada evaluated adolescents and adults with prolonged cough (Senzilet LD et al., Clin Infect Dis 2001;32:1691–7). Overall, 20% had laboratory evidence of pertussis. Culture or PCR tests were positive in only 1%; the remainder were diagnosed by antibody tests, either a four-fold increase in titer or a single titer > 3 standard deviations above the mean for age-matched controls. The clues to pertussis in these patients were a long duration of cough and vomiting with the cough. Pertussis was identified as the cause of the cough in 33% of those aged 12–19 years, 19% of those aged 20–29 years, 19% of those aged 40–59 years, and 16% of older patients. An accompanying editorial by KM Edwards (Clin Infect Dis 2001;32:1698–9) points out the well-known difficulty in culturing the organism or detecting it by PCR. Four-fold rises in antibody titer are difficult to document because, by the time the diagnosis is entertained, the antibody titers are already elevated. Therefore, the approach used for most of the patients in this study, i.e., the requirement that levels be shown to be two to three standard deviations above those in asymptomatic patients of a similar age, has been recommended. This study confirms several others that conclude that, in adults with prolonged cough and no appreciable fever or pulmonary infiltrates, pertussis is the cause in some 20–30%. Amphotericin by Continuous Infusion A randomized, nonblinded study in a Swiss hospital compared the toxicity of amphotericin B deoxycholate by continuous infusion over 24 hours with rapid infusion over 4 hours in neutropenic patients with suspected fungal infection. No antipyretic drugs were permitted on a routine basis. Forty patients were enrolled in each limb. The median number of days of treatment was 12 in the rapid infusion group and 16 in the continuous infusion group. There was a trend toward longer duration and higher cumulative dosage among the continuous infusion patients, but the differences were not significant. Chills or rigors occurred in 63% of patients in the rapid infusion group as opposed to 20% in the continuous infusion group (p < 0.0001), and similar differences between the groups were noted in the incidence of vomiting and the need for antipyretic drugs. There were far more interruptions of treatment or dosage reductions and a greater incidence of impairment of renal function in the rapid infusion group. There were seven deaths in the rapid infusion group (most with pneumonia due to fungal or Pneumocystis carinii pneumonia) and none in the continuous infusion group. After 3 months follow-up, there were 12 deaths in the rapid infusion group and 4 in the continuous infusion group. The authors point out that the magnitude of the benefit from continuous infusion was of the same order as that obtained with liposomal amphotericin B—which makes sense in that much of the benefit of liposomal formulations may rest on the delay in the interaction between the drug and receptor sites. This study is extremely important. It should either be repeated for confirmation or a direct comparison should be made between continuous infusion and liposomal amphotericin. If continuous infusion of amphotericin B deoxycholate is as nontoxic as the expensive liposomal formulations, the savings achieved from continuous infusion could be substantial. Foot-and-Mouth Disease Vaccine The June issue of ASM News (Stencel C, ASM News 2001;67:290–2) contained interesting information about foot-and-mouth disease, especially regarding efforts to develop an effective vaccine. Picornaviridae viruses are able to spread by aerosol for many miles, and as few as 10 virions can infect. For reasons not well understood, the virus tends to persist in infected animals long after symptomatic recovery from infection. The virus readily mutates: there are at least seven major serotypes and 60 subtypes of the virus. A vaccine would be type-specific, limiting its utility. Moreover, vaccines studied to date prevent symptoms but do not block infection or transmission. Complicating efforts at detection, serological methods do not distinguish between vaccine-induced and infection-induced antibodies. The immunity from vaccines wears off quickly, requiring annual or semi-annual revaccination. Finally, production costs would be high because high-level containment facilities would have to be used. Alternatives to killed virus vaccines are being studied, especially empty virus capsids using a replication-defective adenovirus vector. This approach has the potential advantage of lower production costs, the capability of incorporating epitopes from several serotypes, and the capability to allow easy distinction between antibodies to the natural infection and to the vaccine. However, it remains unclear if this or any other vaccine can reduce the problem of viral persistence. This may require the additional use of antiviral drugs or cytokine treatment.

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